For many people suffering from disabling conditions, such as Parkinsons disease, spinal injury and paralysis, heart disease, and even cancer, announcements in the press around breakthroughs in stem cell research undoubtedly bring hope.

Keeping the balance between hope and hype is a difficult one, particularly when there are vulnerable and suffering people relying on the hope medical research offers. As Australian of the Year, Emeritus Professor Alan Mackay-Sim, stated in his acceptance speech, there are now many clinical trials being performed in Australia and around the globe, to determine whether the delivery of certain types of cells, including some grown from stem cells, into the spinal column can allow patients with spinal cord injury to regain function.

For these individuals, even a small gain of functionis a major advance. However, as yet there is no stem cell silver bullet.

And stem cells that have shown promise can also cause complications. It was also reported a paraplegic woman developed a growth in her spine many years after an unsuccessful spinal stem cell treatmentHence, more research to test these and other types of cells in well-run clinical trials is required to move from anecdote to safe and effective therapies.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:The future of stem cells: tackling hype versus hope

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The primary focus of the Disabled World web site is to provide up to date information via our informative articles, disability news and educational videos. In addition to stories by our in-house writers and news items by disability organizations and Government Departments, each day we manually select relevant items that we consider will be of interest to persons with disabilities, carers, and the general public. Submission of disability related information, press releases and events are welcome.

The word "disabled" is defined as having a physical or mental disability : unable to perform one or more natural activities (such as walking or seeing) because of illness, injury, etc.

The word disabled came to be used as the standard term in referring to people with physical or mental disabilities in the second half of the 20th century - and it remains the most generally accepted term in both British and US English. Lately, "Disability" and "Disabled" are terms that are undergoing change due to the disability rights movement in the U.S. and U.K. - Disability or Disabled - Which Term is Right?

"People with disabilities are the largest minority group, the only one any person can join at any time."

Disability is a subject you may read about online, or in a newspaper, but not think of as something that might actually happen to you. But your chances of becoming disabled are greater than you realize. Today more people live with a disability than ever before due to our aging societies as well as improved medical treatments helping manage long-term health problems.

Some people are born with a disability, others become disabled as a result of an illness or injury, and some people develop them as they age. At some point in our lives almost all of us will have some type of disability.

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One of the key challenges for a person with a disability is to be seen by the public, to be portrayed in media outlets, and treated by health care professionals, as an individual with their own abilities, not just stereotyped as a "disabled person".

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This article is about birth in humans. For birth in other mammals, see birth.

Childbirth, also known as labour and delivery, is the ending of a pregnancy by one or more babies leaving a woman's uterus.[1] In 2015 there were about 135 million births globally.[2] About 15 million were born before 37 weeks of gestation,[3] while between 3 and 12% were born after 42 weeks.[4] In the developed world most deliveries occur in hospital,[5][6] while in the developing world most births take place at home with the support of a traditional birth attendant.[7]

The most common way of childbirth is a vaginal delivery.[8] It involves three stages of labour: the shortening and opening of the cervix, descent and birth of the baby, and the pushing out of the placenta.[9] The first stage typically lasts twelve to nineteen hours, the second stage twenty minutes to two hours, and the third stage five to thirty minutes.[10] The first stage begins with crampy abdominal or back pains that last around half a minute and occur every ten to thirty minutes.[9] The crampy pains become stronger and closer together over time.[10] During the second stage pushing with contractions may occur.[10] In the third stage delayed clamping of the umbilical cord is generally recommended.[11] A number of methods can help with pain such as relaxation techniques, opioids, and spinal blocks.[10]

Most babies are born head first; however about 4% are born feet or buttock first, known as breech.[10][12] During labour a women can generally eat and move around as she likes, pushing is not recommended during the first stage or during delivery of the head, and enemas are not recommended.[13] While making a cut to the opening of the vagina is common, known as an episiotomy, it is generally not needed.[10] In 2012, about 23 million deliveries occurred by a surgical procedure known as Caesarean section.[14] Caesarean sections may be recommended for twins, signs of distress in the baby, or breech position.[10] This method of delivery can take longer to heal from.[10]

Each year complications from pregnancy and childbirth result in about 500,000 maternal deaths, 7 million women have serious long term problems, and 50 million women have health negative outcomes following delivery.[15] Most of these occur in the developing world.[15] Specific complications include obstructed labour, postpartum bleeding, eclampsia, and postpartum infection.[15] Complications in the baby include birth asphyxia.[16]

The most prominent sign of labour is strong repetitive uterine contractions. The distress levels reported by labouring women vary widely. They appear to be influenced by fear and anxiety levels, experience with prior childbirth, cultural ideas of childbirth and pain,[17][18] mobility during labour, and the support received during labour. Personal expectations, the amount of support from caregivers, quality of the caregiver-patient relationship, and involvement in decision-making are more important in women's overall satisfaction with the experience of childbirth than are other factors such as age, socioeconomic status, ethnicity, preparation, physical environment, pain, immobility, or medical interventions.[19]

Pain in contractions has been described as feeling similar to very strong menstrual cramps. Women are often encouraged to refrain from screaming, but moaning and grunting may be encouraged to help lessen pain. Crowning may be experienced as an intense stretching and burning. Even women who show little reaction to labour pains, in comparison to other women, show a substantially severe reaction to crowning.

Back labour is a term for specific pain occurring in the lower back, just above the tailbone, during childbirth.[20]

Childbirth can be an intense event and strong emotions, both positive and negative, can be brought to the surface. Abnormal and persistent fear of childbirth is known as tokophobia.

During the later stages of gestation there is an increase in abundance of oxytocin, a hormone that is known to evoke feelings of contentment, reductions in anxiety, and feelings of calmness and security around the mate.[21] Oxytocin is further released during labour when the fetus stimulates the cervix and vagina, and it is believed that it plays a major role in the bonding of a mother to her infant and in the establishment of maternal behavior. The act of nursing a child also causes a release of oxytocin.[22]

Between 70% and 80% of mothers in the United States report some feelings of sadness or "baby blues" after giving birth. The symptoms normally occur for a few minutes up to few hours each day and they should lessen and disappear within two weeks after delivery. Postpartum depression may develop in some women; about 10% of mothers in the United States are diagnosed with this condition. Preventive group therapy has proven effective as a prophylactic treatment for postpartum depression.[23][24]

Humans are bipedal with an erect stance. The erect posture causes the weight of the abdominal contents to thrust on the pelvic floor, a complex structure which must not only support this weight but allow, in women, three channels to pass through it: the urethra, the vagina and the rectum. The infant's head and shoulders must go through a specific sequence of maneuvers in order to pass through the ring of the mother's pelvis.

Six phases of a typical vertex (head-first presentation) delivery:

Station refers to the relationship of the fetal presenting part to the level of the ischial spines. When the presenting part is at the ischial spines the station is 0 (synonymous with engagement). If the presenting fetal part is above the spines, the distance is measured and described as minus stations, which range from 1 to 4cm. If the presenting part is below the ischial spines, the distance is stated as plus stations ( +1 to +4cm). At +3 and +4 the presenting part is at the perineum and can be seen.[25]

The fetal head may temporarily change shape substantially (becoming more elongated) as it moves through the birth canal. This change in the shape of the fetal head is called molding and is much more prominent in women having their first vaginal delivery.[26]

There are various definitions of the onset of labour, including:

In order to avail for more uniform terminology, the first stage of labour is divided into "latent" and "active" phases, where the latent phase is sometimes included in the definition of labour,[30] and sometimes not.[31]

Some reports note that the onset of term labour more commonly takes place in the late night and early morning hours. This may be a result of a synergism between the nocturnal increase in melatonin and oxytocin.[32]

The latent phase of labour is also called the quiescent phase, prodromal labour, or pre-labour. It is a subclassification of the first stage.[33]

The latent phase is generally defined as beginning at the point at which the woman perceives regular uterine contractions.[34] In contrast, Braxton Hicks contractions, which are contractions that may start around 26 weeks gestation and are sometimes called "false labour", should be infrequent, irregular, and involve only mild cramping.[35] The signaling mechanisms responsible for uterine coordination are complex. Electrical propagation is the primary mechanism used for signaling up to several centimeters. Over longer distances, however, signaling may involve a mechanical mechanism.[36]

Cervical effacement, which is the thinning and stretching of the cervix, and cervical dilation occur during the closing weeks of pregnancy and is usually complete or near complete, by the end of the latent phase.[citation needed] The degree of cervical effacement may be felt during a vaginal examination. A 'long' cervix implies that effacement has not yet occurred. Latent phase ends with the onset of active first stage, and this transition is defined retrospectively.

The active stage of labour (or "active phase of first stage" if the previous phase is termed "latent phase of first stage") has geographically differing definitions. In the US, the definition of active labour was changed from 3 to 4cm, to 5cm of cervical dilation for multiparous women, mothers who had given birth previously, and at 6cm for nulliparous women, those who had not given birth before.[37] This has been done in an effort to increase the rates of vaginal delivery.[38]

A definition of active labour in a British journal was having contractions more frequent than every 5 minutes, in addition to either a cervical dilation of 3cm or more or a cervical effacement of 80% or more.[39]

In Sweden, the onset of the active phase of labour is defined as when two of the following criteria are met:[40]

Health care providers may assess a labouring mother's progress in labour by performing a cervical exam to evaluate the cervical dilation, effacement, and station. These factors form the Bishop score. The Bishop score can also be used as a means to predict the success of an induction of labour.

During effacement, the cervix becomes incorporated into the lower segment of the uterus. During a contraction, uterine muscles contract causing shortening of the upper segment and drawing upwards of the lower segment, in a gradual expulsive motion.[citation needed] The presenting fetal part then is permitted to descend. Full dilation is reached when the cervix has widened enough to allow passage of the baby's head, around 10cm dilation for a term baby.

The duration of labour varies widely, but the active phase averages some 8 hours[41] for women giving birth to their first child ("primiparae") and shorter for women who have already given birth ("multiparae"). Active phase prolongation is defined as in a primigravid woman as the failure of the cervix to dilate at a rate of 1.2cm/h over a period of at least two hours. This definition is based on Friedman's Curve, which plots the typical rate of cervical dilation and fetal descent during active labour.[42] Some practitioners may diagnose "Failure to Progress", and consequently, propose interventions to optimize chances for healthy outcome.[43]

The expulsion stage (stimulated by prostaglandins and oxytocin) begins when the cervix is fully dilated, and ends when the baby is born. As pressure on the cervix increases, women may have the sensation of pelvic pressure and an urge to begin pushing. At the beginning of the normal second stage, the head is fully engaged in the pelvis; the widest diameter of the head has passed below the level of the pelvic inlet. The fetal head then continues descent into the pelvis, below the pubic arch and out through the vaginal introitus (opening). This is assisted by the additional maternal efforts of "bearing down" or pushing. The appearance of the fetal head at the vaginal orifice is termed the "crowning". At this point, the woman will feel an intense burning or stinging sensation.

When the amniotic sac has not ruptured during labour or pushing, the infant can be born with the membranes intact. This is referred to as "delivery en caul".

Complete expulsion of the baby signals the successful completion of the second stage of labour.

The second stage of birth will vary by factors including parity (the number of children a woman has had), fetal size, anesthesia, and the presence of infection. Longer labours are associated with declining rates of spontaneous vaginal delivery and increasing rates of infection, perineal laceration, and obstetric hemorrhage, as well as the need for intensive care of the neonate.[44]

The period from just after the fetus is expelled until just after the placenta is expelled is called the third stage of labour or the involution stage. Placental expulsion begins as a physiological separation from the wall of the uterus. The average time from delivery of the baby until complete expulsion of the placenta is estimated to be 1012 minutes dependent on whether active or expectant management is employed[45] In as many as 3% of all vaginal deliveries, the duration of the third stage is longer than 30 minutes and raises concern for retained placenta.[46]

Placental expulsion can be managed actively or it can be managed expectantly, allowing the placenta to be expelled without medical assistance. Active management is described as the administration of a uterotonic drug within one minute of fetal delivery, controlled traction of the umbilical cord and fundal massage after delivery of the placenta, followed by performance of uterine massage every 15 minutes for two hours.[47] In a joint statement, World Health Organization, the International Federation of Gynaecology and Obstetrics and the International Confederation of Midwives recommend active management of the third stage of labour in all vaginal deliveries to help to prevent postpartum hemorrhage.[48][49][50]

Delaying the clamping of the umbilical cord until at least one minute after birth improves outcomes as long as there is the ability to treat jaundice if it occurs.[51] In some birthing centers, this may be delayed by 5 minutes or more, or omitted entirely. Delayed clamping of the cord decreases the risk of anemia but may increase risk of jaundice. Clamping is followed by cutting of the cord, which is painless due to the absence of nerves.

The "fourth stage of labour" is the period beginning immediately after the birth of a child and extending for about six weeks. The terms postpartum and postnatal are often used to describe this period.[52] It is the time in which the mother's body, including hormone levels and uterus size, return to a non-pregnant state and the newborn adjusts to life outside the mother's body. The World Health Organization (WHO) describes the postnatal period as the most critical and yet the most neglected phase in the lives of mothers and babies; most deaths occur during the postnatal period.[53]

Following the birth, if the mother had an episiotomy or a tearing of the perineum, it is stitched. The mother should have regular assessments for uterine contraction and fundal height,[54] vaginal bleeding, heart rate and blood pressure, and temperature, for the first 24 hours after birth. The first passing of urine should be documented within 6 hours.[53] Afterpains (pains similar to menstrual cramps), contractions of the uterus to prevent excessive blood flow, continue for several days. Vaginal discharge, termed "lochia", can be expected to continue for several weeks; initially bright red, it gradually becomes pink, changing to brown, and finally to yellow or white.[55]

Most authorities suggest the infant be placed in skin-to-skin contact with the mother for 1 2 hours immediately after birth, putting routine cares off till later.

Until recently babies born in hospitals were removed from their mothers shortly after birth and brought to the mother only at feeding times. Mothers were told that their newborn would be safer in the nursery and that the separation would offer the mother more time to rest. As attitudes began to change, some hospitals offered a "rooming in" option wherein after a period of routine hospital procedures and observation, the infant could be allowed to share the mother's room. However, more recent information has begun to question the standard practice of removing the newborn immediately postpartum for routine postnatal procedures before being returned to the mother. Beginning around 2000, some authorities began to suggest that early skin-to-skin contact (placing the naked baby on the mother's chest) may benefit both mother and infant. Using animal studies that have shown that the intimate contact inherent in skin-to-skin contact promotes neurobehaviors that result in the fulfillment of basic biological needs as a model, recent studies have been done to assess what, if any, advantages may be associated with early skin-to-skin contact for human mothers and their babies. A 2011 medical review looked at existing studies and found that early skin-to-skin contact, sometimes called kangaroo care, resulted in improved breastfeeding outcomes, cardio-respiratory stability, and a decrease in infant crying. [56][57][58] A 2007 Cochrane review of studies found that skin-to-skin contact at birth reduced crying, kept the baby warmer, improved mother-baby interaction, and improved the chances for successful breastfeeding.[59]

As of 2014, early postpartum skin-to-skin contact is endorsed by all major organizations that are responsible for the well-being of infants, including the American Academy of Pediatrics.[60] The World Health Organization (WHO) states that "the process of childbirth is not finished until the baby has safely transferred from placental to mammary nutrition." They advise that the newborn be placed skin-to-skin with the mother, postponing any routine procedures for at least one to two hours. The WHO suggests that any initial observations of the infant can be done while the infant remains close to the mother, saying that even a brief separation before the baby has had its first feed can disturb the bonding process. They further advise frequent skin-to-skin contact as much as possible during the first days after delivery, especially if it was interrupted for some reason after the delivery.[61] The National Institute for Health and Care Excellence also advises postponing procedures such as weighing, measuring, and bathing for at least 1 hour to insure an initial period of skin-to-skin contact between mother and infant. [62]

Deliveries are assisted by a number of professions include: obstetricians, family physicians and midwives. For low risk pregnancies all three result in similar outcomes.[63]

Eating or drinking during labour is an area of ongoing debate. While some have argued that eating in labour has no harmful effects on outcomes,[64] others continue to have concern regarding the increased possibility of an aspiration event (choking on recently eaten foods) in the event of an emergency delivery due to the increased relaxation of the esophagus in pregnancy, upward pressure of the uterus on the stomach, and the possibility of general anesthetic in the event of an emergency cesarean.[65] A 2013 Cochrane review found that with good obstetrical anaesthesia there is no change in harms from allowing eating and drinking during labour in those who are unlikely to need surgery. They additionally acknowledge that not eating does not mean there is an empty stomach or that its contents are not as acidic. They therefore conclude that "women should be free to eat and drink in labour, or not, as they wish."[66]

At one time shaving of the area around the vagina, was common practice due to the belief that hair removal reduced the risk of infection, made an episiotomy (a surgical cut to enlarge the vaginal entrance) easier, and helped with instrumental deliveries. It is currently less common, though it is still a routine procedure in some countries. A 2009 Cochrane review found no evidence of any benefit with perineal shaving. The review did find side effects including irritation, redness, and multiple superficial scratches from the razor.[67][needs update] Another effort to prevent infection has been the use of the antiseptic chlorhexidine or providone-iodine solution in the vagina. Evidence of benefit with chlorhexidine is lacking.[68] A decreased risk is found with providone-iodine when a cesarean section is to be performed.[69]

Active management of labour consists of a number of care principles, including frequent assessment of cervical dilatation. If the cervix is not dilating, oxytocin is offered. This management results in a slightly reduced number of caesarean births, but does not change how many women have assisted vaginal births. 75% of women report that they are very satisfied with either active management or normal care.[70]

In many cases and with increasing frequency, childbirth is achieved through induction of labour or caesarean section. Caesarean section is the removal of the neonate through a surgical incision in the abdomen, rather than through vaginal birth.[71] Childbirth by C-Sections increased 50% in the U.S. from 1996 to 2006, and comprise nearly 32% of births in the U.S. and Canada.[71][72] Induced births and elective cesarean before 39 weeks can be harmful to the neonate as well as harmful or without benefit to the mother. Therefore, many guidelines recommend against non-medically required induced births and elective cesarean before 39 weeks.[73] The rate of labour induction in the United States is 22%, and has more than doubled from 1990 to 2006.[74][75]

Health conditions that may warrant induced labour or cesarean delivery include gestational or chronic hypertension, preeclampsia, eclampsia, diabetes, premature rupture of membranes, severe fetal growth restriction, and post-term pregnancy. Cesarean section too may be of benefit to both the mother and baby for certain indications including maternal HIV/AIDS, fetal abnormality, breech position, fetal distress, multiple gestations, and maternal medical conditions which would be worsened by labour or vaginal birth.

Pitocin is the most commonly used agent for induction in the United States, and is used to induce uterine contractions. Other methods of inducing labour include stripping of the amniotic membrane, artificial rupturing of the amniotic sac (called amniotomy), or nipple stimulation. Ripening of the cervix can be accomplished with the placement of a Foley catheter or the use of synthetic prostaglandins such as misoprostol.[74] A large review of methods of induction was published in 2011.[76]

The American Congress of Obstetricians and Gynecologists (ACOG) guidelines recommend a full evaluation of the maternal-fetal status, the status of the cervix, and at least a 39 completed weeks (full term) of gestation for optimal health of the newborn when considering elective induction of labour. Per these guidelines, the following conditions may be an indication for induction, including:

Induction is also considered for logistical reasons, such as the distance from hospital or psychosocial conditions, but in these instances gestational age confirmation must be done, and the maturity of the fetal lung must be confirmed by testing.

The ACOG also note that contraindications for induced labour are the same as for spontaneous vaginal delivery, including vasa previa, complete placenta praevia, umbilical cord prolapse or active genital herpes simplex infection.[77]

Some women prefer to avoid analgesic medication during childbirth. Psychological preparation may be beneficial. A recent Cochrane overview of systematic reviews on non-drug interventions found that relaxation techniques, immersion in water, massage, and acupuncture may provide pain relief. Acupuncture and relaxation were found to decrease the number of caesarean sections required.[78] Immersion in water has been found to relieve pain during the first stage of labor and to reduce the need for anesthesia and shorten the duration of labor, however the safety and efficacy of immersion during birth, water birth, has not been established or associated with maternal or fetal benefit.[79]

Some women like to have someone to support them during labour and birth; such as a midwife, nurse, or doula; or a lay person such as the father of the baby, a family member, or a close friend. Studies have found that continuous support during labor and delivery reduce the need for medication and a caesarean or operative vaginal delivery, and result in an improved Apgar score for the infant.[80][81]

The injection of small amounts of sterile water into or just below the skin at several points on the back has been a method tried to reduce labour pain, but no good evidence shows that it actually helps.[82]

Different measures for pain control have varying degrees of success and side effects to the woman and her baby. In some countries of Europe, doctors commonly prescribe inhaled nitrous oxide gas for pain control, especially as 53% nitrous oxide, 47% oxygen, known as Entonox; in the UK, midwives may use this gas without a doctor's prescription. Opioids such as fentanyl may be used, but if given too close to birth there is a risk of respiratory depression in the infant.

Popular medical pain control in hospitals include the regional anesthetics epidurals (EDA), and spinal anaesthesia. Epidural analgesia is a generally safe and effective method of relieving pain in labour, but is associated with longer labour, more operative intervention (particularly instrument delivery), and increases in cost.[83] Generally, pain and stress hormones rise throughout labour for women without epidurals, while pain, fear, and stress hormones decrease upon administration of epidural analgesia, but rise again later.[84] Medicine administered via epidural can cross the placenta and enter the bloodstream of the fetus.[85] Epidural analgesia has no statistically significant impact on the risk of caesarean section, and does not appear to have an immediate effect on neonatal status as determined by Apgar scores.[86]

Augmentation is the process of facilitating further labour. Oxytocin has been used to increase the rate of vaginal delivery in those with a slow progress of labour.[87]

Administration of antispasmodics (e.g. hyoscine butylbromide) is not formally regarded as augmentation of labour; however, there is weak evidence that they may shorten labour.[88] There is not enough evidence to make conclusions about unwanted effects in mothers or babies.[88]

Vaginal tears can occur during childbirth, most often at the vaginal opening as the baby's head passes through, especially if the baby descends quickly. Tears can involve the perineal skin or extend to the muscles and the anal sphincter and anus. The midwife or obstetrician may decide to make a surgical cut to the perineum (episiotomy) to make the baby's birth easier and prevent severe tears that can be difficult to repair. A 2012 Cochrane review compared episiotomy as needed (restrictive) with routine episiotomy to determine the possible benefits and harms for mother and baby. The review found that restrictive episiotomy policies appeared to give a number of benefits compared with using routine episiotomy. Women experienced less severe perineal trauma, less posterior perineal trauma, less suturing and fewer healing complications at seven days with no difference in occurrence of pain, urinary incontinence, painful sex or severe vaginal/perineal trauma after birth, however they found that women experienced more anterior perineal damage with restrictive episiotomy.[89]

Obstetric forceps or ventouse may be used to facilitate childbirth.

In cases of a cephalic presenting twin (first baby head down), twins can often be delivered vaginally. In some cases twin delivery is done in a larger delivery room or in an operating theatre, in the event of complication e.g.

Historically women have been attended and supported by other women during labour and birth. However currently, as more women are giving birth in a hospital rather than at home, continuous support has become the exception rather than the norm. When women became pregnant any time before the 1950s the husband would not be in the birthing room. It did not matter if it was a home birth; the husband was waiting downstairs or in another room in the home. If it was in a hospital then the husband was in the waiting room. "Her husband was attentive and kind, but, Kirby concluded, Every good woman needs a companion of her own sex."[90] Obstetric care frequently subjects women to institutional routines, which may have adverse effects on the progress of labour. Supportive care during labour may involve emotional support, comfort measures, and information and advocacy which may promote the physical process of labour as well as women's feelings of control and competence, thus reducing the need for obstetric intervention. The continuous support may be provided either by hospital staff such as nurses or midwives, doulas, or by companions of the woman's choice from her social network. There is increasing evidence to show that the participation of the child's father in the birth leads to better birth and also post-birth outcomes, providing the father does not exhibit excessive anxiety.[91]

A recent Cochrane review involving more than 15,000 women in a wide range of settings and circumstances found that "Women who received continuous labour support were more likely to give birth 'spontaneously', i.e. give birth with neither caesarean nor vacuum nor forceps. In addition, women were less likely to use pain medications, were more likely to be satisfied, and had slightly shorter labours. Their babies were less likely to have low five-minute Apgar scores."[80]

For monitoring of the fetus during childbirth, a simple pinard stethoscope or doppler fetal monitor ("doptone") can be used. A method of external (noninvasive) fetal monitoring (EFM) during childbirth is cardiotocography, using a cardiotocograph that consists of two sensors: The heart (cardio) sensor is an ultrasonic sensor, similar to a Doppler fetal monitor, that continuously emits ultrasound and detects motion of the fetal heart by the characteristic of the reflected sound. The pressure-sensitive contraction transducer, called a tocodynamometer (toco) has a flat area that is fixated to the skin by a band around the belly. The pressure required to flatten a section of the wall correlates with the internal pressure, thereby providing an estimate of contraction[92] Monitoring with a cardiotocograph can either be intermittent or continuous.

A mother's water has to break before internal (invasive) monitoring can be used. More invasive monitoring can involve a fetal scalp electrode to give an additional measure of fetal heart activity, and/or intrauterine pressure catheter (IUPC). It can also involve fetal scalp pH testing.

It is currently possible to collect two types of stem cells during childbirth: amniotic stem cells and umbilical cord blood stem cells.[93] They are being studied as possible treatments of a number of conditions.[93]

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The "natural" maternal mortality rate of childbirthwhere nothing is done to avert maternal deathhas been estimated at 1500 deaths per 100,000 births.[95] (See main articles: neonatal death, maternal death). Each year about 500,000 women die due to pregnancy, 7 million have serious long term complications, and 50 million have negative outcomes following delivery.[15]

Modern medicine has decreased the risk of childbirth complications. In Western countries, such as the United States and Sweden, the current maternal mortality rate is around 10 deaths per 100,000 births.[95]:p.10 As of June 2011, about one third of American births have some complications, "many of which are directly related to the mother's health."[96]

Birthing complications may be maternal or fetal, and long term or short term.

Newborn mortality at 37 weeks may be 2.5 times the number at 40 weeks, and was elevated compared to 38 weeks of gestation. These "early term" births were also associated with increased death during infancy, compared to those occurring at 39 to 41 weeks ("full term").[73] Researchers found benefits to going full term and "no adverse effects" in the health of the mothers or babies.[73]

Medical researchers find that neonates born before 39 weeks experienced significantly more complications (2.5 times more in one study) compared with those delivered at 39 to 40 weeks. Health problems among babies delivered "pre-term" included respiratory distress, jaundice and low blood sugar.[73][97] The American Congress of Obstetricians and Gynecologists and medical policy makers review research studies and find increased incidence of suspected or proven sepsis, RDS, Hypoglycemia, need for respiratory support, need for NICU admission, and need for hospitalization > 4 5 days. In the case of cesarean sections, rates of respiratory death were 14 times higher in pre-labour at 37 compared with 40 weeks gestation, and 8.2 times higher for pre-labour cesarean at 38 weeks. In this review, no studies found decreased neonatal morbidity due to non-medically indicated (elective) delivery before 39 weeks.[73]

The second stage of labour may be delayed or lengthy due to:

Secondary changes may be observed: swelling of the tissues, maternal exhaustion, fetal heart rate abnormalities. Left untreated, severe complications include death of mother and/or baby, and genitovaginal fistula.

Obstructed labour, also known as labor dystocia, is when, even though the uterus is contracting normally, the baby does not exit the pelvis during childbirth due to being physically blocked.[98] Prolonged obstructed labor can result in obstetric fistula, a complication of childbirth where tissue death preforates the rectum or bladder.

Vaginal birth injury with visible tears or episiotomies are common. Internal tissue tearing as well as nerve damage to the pelvic structures lead in a proportion of women to problems with prolapse, incontinence of stool or urine and sexual dysfunction. Fifteen percent of women become incontinent, to some degree, of stool or urine after normal delivery, this number rising considerably after these women reach menopause. Vaginal birth injury is a necessary, but not sufficient, cause of all non hysterectomy related prolapse in later life. Risk factors for significant vaginal birth injury include:

There is tentative evidence that antibiotics may help prevent wound infections in women with third or fourth degree tears.[99]

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Childbirth - Wikipedia

Spinal Cord Stem Cells Comments Off on Childbirth – Wikipedia | January 13th, 2017

The central nervous system (CNS) is the part of the nervous system consisting of the brain and spinal cord. The central nervous system is so named because it integrates information it receives from, and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric animalsthat is, all multicellular animals except sponges and radially symmetric animals such as jellyfishand it contains the majority of the nervous system. Many consider the retina[2] and the optic nerve (2nd cranial nerve),[3][4] as well as the olfactory nerves (1st) and olfactory epithelium[5] as parts of the CNS, synapsing directly on brain tissue without intermediate ganglia. Following this classification[which?] the olfactory epithelium is the only central nervous tissue in direct contact with the environment, which opens up for therapeutic treatments. [5] The CNS is contained within the dorsal body cavity, with the brain housed in the cranial cavity and the spinal cord in the spinal canal. In vertebrates, the brain is protected by the skull, while the spinal cord is protected by the vertebrae, both enclosed in the meninges.[6]

The central nervous system consists of the two major structures: the brain and spinal cord. The brain is encased in the skull, and protected by the cranium.[7] The spinal cord is continuous with the brain and lies caudally to the brain,[8] and is protected by the vertebra.[7] The spinal cord reaches from the base of the skull, continues through[7] or starting below[9] the foramen magnum,[7] and terminates roughly level with the first or second lumbar vertebra,[8][9] occupying the upper sections of the vertebral canal.[4]

Microscopically, there are differences between the neurons and tissue of the central nervous system and the peripheral nervous system.[citation needed] The central nervous system is divided in white and gray matter.[8] This can also be seen macroscopically on brain tissue. The white matter consists of axons and oligodendrocytes, while the gray matter consists of neurons and unmyelinated fibers. Both tissues include a number of glial cells (although the white matter contains more), which are often referred to as supporting cells of the central nervous system. Different forms of glial cells have different functions, some acting almost as scaffolding for neuroblasts to climb during neurogenesis such as bergmann glia, while others such as microglia are a specialized form of macrophage, involved in the immune system of the brain as well as the clearance of various metabolites from the brain tissue.[4]Astrocytes may be involved with both clearance of metabolites as well as transport of fuel and various beneficial substances to neurons from the capillaries of the brain. Upon CNS injury astrocytes will proliferate, causing gliosis, a form of neuronal scar tissue, lacking in functional neurons.[4]

The brain (cerebrum as well as midbrain and hindbrain) consists of a cortex, composed of neuron-bodies constituting gray matter, while internally there is more white matter that form tracts and commissures. Apart from cortical gray matter there is also subcortical gray matter making up a large number of different nuclei.[8]

From and to the spinal cord are projections of the peripheral nervous system in the form of spinal nerves (sometimes segmental nerves[7]). The nerves connect the spinal cord to skin, joints, muscles etc. and allow for the transmission of efferent motor as well as afferent sensory signals and stimuli.[8] This allows for voluntary and involuntary motions of muscles, as well as the perception of senses. All in all 31 spinal nerves project from the brain stem,[8] some forming plexa as they branch out, such as the brachial plexa, sacral plexa etc.[7] Each spinal nerve will carry both sensory and motor signals, but the nerves synapse at different regions of the spinal cord, either from the periphery to sensory relay neurons that relay the information to the CNS or from the CNS to motor neurons, which relay the information out.[8]

The spinal cord relays information up to the brain through spinal tracts through the "final common pathway"[8] to the thalamus and ultimately to the cortex. Not all information is relayed to the cortex, and does not reach our immediate consciousness, but is instead transmitted only to the thalamus which sorts and adapts accordingly. This in turn may explain why we are not constantly aware of all aspects of our surroundings.[citation needed]

Schematic image showing the locations of a few tracts of the spinal cord.

Reflexes may also occur without engaging more than one neuron of the central nervous system as in the below example of a short reflex.

Apart from the spinal cord, there are also peripheral nerves of the PNS that synapse through intermediaries or ganglia directly on the CNS. These 12 nerves exist in the head and neck region and are called cranial nerves. Cranial nerves bring information to the CNS to and from the face, as well as to certain muscles (such as the trapezius muscle, which is innervated by accessory nerves[7] as well as certain cervical spinal nerves).[7]

Two pairs of cranial nerves; the olfactory nerves and the optic nerves[2] are often considered structures of the central nervous system. This is because they do not synapse first on peripheral ganglia, but directly on central nervous neurons. The olfactory epithelium is significant in that it consists of central nervous tissue expressed in direct contact to the environment, allowing for administration of certain pharmaceuticals and drugs. [5]

Myelinated peripheral nerve at top, central nervous neuron at bottom

Rostrally to the spinal cord lies the brain.[8] The brain makes up the largest portion of the central nervous system, and is often the main structure referred to when speaking of the nervous system. The brain is the major functional unit of the central nervous system. While the spinal cord has certain processing ability such as that of spinal locomotion and can process reflexes, the brain is the major processing unit of the nervous system.[citation needed]

The brainstem consists of the medulla, the pons and the midbrain. The medulla can be referred to as an extension of the spinal cord, and its organization and functional properties are similar to those of the spinal cord.[8] The tracts passing from the spinal cord to the brain pass through here.[8]

Regulatory functions of the medulla nuclei include control of the blood pressure and breathing. Other nuclei are involved in balance, taste, hearing and control of muscles of the face and neck.[8]

The next structure rostral to the medulla is the pons, which lies on the ventral anterior side of the brainstem. Nuclei in the pons include pontine nuclei which work with the cerebellum and transmit information between the cerebellum and the cerebral cortex.[8] In the dorsal posterior pons lie nuclei that have to do with breathing, sleep and taste.[8]

The midbrain (or mesencephalon) is situated above and rostral to the pons, and includes nuclei linking distinct parts of the motor system, among others the cerebellum, the basal ganglia and both cerebral hemispheres. Additionally parts of the visual and auditory systems are located in the mid brain, including control of automatic eye movements.[8]

The brainstem at large provides entry and exit to the brain for a number of pathways for motor and autonomic control of the face and neck through cranial nerves,[8] and autonomic control of the organs is mediated by the tenth cranial (vagus) nerve.[4] A large portion of the brainstem is involved in such autonomic control of the body. Such functions may engage the heart, blood vessels, pupillae, among others.[8]

The brainstem also hold the reticular formation, a group of nuclei involved in both arousal and alertness.[8]

The cerebellum lies behind the pons. The cerebellum is composed of several dividing fissures and lobes. Its function includes the control of posture, and the coordination of movements of parts of the body, including the eyes and head as well as the limbs. Further it is involved in motion that has been learned and perfected though practice, and will adapt to new learned movements.[8] Despite its previous classification as a motor structure, the cerebellum also displays connections to areas of the cerebral cortex involved in language as well as cognitive functions. These connections have been shown by the use of medical imaging techniques such as fMRI and PET.[8]

The body of the cerebellum holds more neurons than any other structure of the brain including that of the larger cerebrum (or cerebral hemispheres), but is also more extensively understood than other structures of the brain, and includes fewer types of different neurons.[8] It handles and processes sensory stimuli, motor information as well as balance information from the vestibular organ.[8]

The two structures of the diencephalon worth noting are the thalamus and the hypothalamus. The thalamus acts as a linkage between incoming pathways from the peripheral nervous system as well as the optical nerve (though it does not receive input from the olfactory nerve) to the cerebral hemispheres. Previously it was considered only a "relay station", but it is engaged in the sorting of information that will reach cerebral hemispheres (neocortex).[8]

Apart from its function of sorting information from the periphery, the thalamus also connects the cerebellum and basal ganglia with the cerebrum. In common with the aforementioned reticular system the thalamus is involved in wakefullness and consciousness, such as though the SCN.[8]

The hypothalamus engages in functions of a number of primitive emotions or feelings such as hunger, thirst and maternal bonding. This is regulated partly through control of secretion of hormones from the pituitary gland. Additionally the hypothalamus plays a role in motivation and many other behaviors of the individual.[8]

The cerebrum of cerebral hemispheres make up the largest visual portion of the human brain. Various structures combine forming the cerebral hemispheres, among others, the cortex, basal ganglia, amygdala and hippocampus. The hemispheres together control a large portion of the functions of the human brain such as emotion, memory, perception and motor functions. Apart from this the cerebral hemispheres stand for the cognitive capabilities of the brain.[8]

Connecting each of the hemispheres is the corpus callosum as well as several additional commissures.[8] One of the most important parts of the cerebral hemispheres is the cortex, made up of gray matter covering the surface of the brain. Functionally, the cerebral cortex is involved in planning and carrying out of everyday tasks.[8]

The hippocampus is involved in storage of memories, the amygdala plays a role in perception and communication of emotion, while the basal ganglia play a major role in the coordination of voluntary movement.[8]

This differentiates the central nervous system from the peripheral nervous system, which consists of neurons, axons and Schwann cells. Oligodendrocytes and Schwann cells have similar functions in the central and peripheral nervous system respectively. Both act to add myelin sheaths to the axons, which acts as a form of insulation allowing for better and faster proliferation of electrical signals along the nerves. Axons in the central nervous system are often very short (barely a few millimeters) and do not need the same degree of isolation as peripheral nerves do. Some peripheral nerves can be over 1m in length, such as the nerves to the big toe. To ensure signals move at sufficient speed, myelination is needed.

The way in which the Schwann cells and oligodendrocytes myelinate nerves differ. A Schwann cell usually myelinates a single axon, completely surrounding it. Sometimes they may myelinate many axons, especially when in areas of short axons.[7] Oligodendrocytes usually myelinate several axons. They do this by sending out thin projections of their cell membrane which envelop and enclose the axon.

Top; CNS as seen in a median section of a 5 week old embryo. Bottom; CNS seen in a median section of a 3 month old embryo.

During early development of the vertebrate embryo, a longitudinal groove on the neural plate gradually deepens and the ridges on either side of the groove (the neural folds) become elevated, and ultimately meet, transforming the groove into a closed tube called the neural tube.[10] The formation of the neural tube is called neurulation. At this stage, the walls of the neural tube contain proliferating neural stem cells in a region called the ventricular zone. The neural stem cells, principally radial glial cells, multiply and generate neurons through the process of neurogenesis, forming the rudiment of the central nervous system.[11]

The neural tube gives rise to both brain and spinal cord. The anterior (or 'rostral') portion of the neural tube initially differentiates into three brain vesicles (pockets): the prosencephalon at the front, the mesencephalon, and, between the mesencephalon and the spinal cord, the rhombencephalon. (By six weeks in the human embryo) the prosencephalon then divides further into the telencephalon and diencephalon; and the rhombencephalon divides into the metencephalon and myelencephalon. The spinal cord is derived from the posterior or 'caudal' portion of the neural tube.

As a vertebrate grows, these vesicles differentiate further still. The telencephalon differentiates into, among other things, the striatum, the hippocampus and the neocortex, and its cavity becomes the first and second ventricles. Diencephalon elaborations include the subthalamus, hypothalamus, thalamus and epithalamus, and its cavity forms the third ventricle. The tectum, pretectum, cerebral peduncle and other structures develop out of the mesencephalon, and its cavity grows into the mesencephalic duct (cerebral aqueduct). The metencephalon becomes, among other things, the pons and the cerebellum, the myelencephalon forms the medulla oblongata, and their cavities develop into the fourth ventricle.[12]

Development of the neural tube

Rhinencephalon, Amygdala, Hippocampus, Neocortex, Basal ganglia, Lateral ventricles

Epithalamus, Thalamus, Hypothalamus, Subthalamus, Pituitary gland, Pineal gland, Third ventricle

Tectum, Cerebral peduncle, Pretectum, Mesencephalic duct

Pons, Cerebellum

Planarians, members of the phylum Platyhelminthes (flatworms), have the simplest, clearly defined delineation of a nervous system into a central nervous system (CNS) and a peripheral nervous system (PNS).[13][14] Their primitive brains, consisting of two fused anterior ganglia, and longitudinal nerve cords form the CNS; the laterally projecting nerves form the PNS. A molecular study found that more than 95% of the 116 genes involved in the nervous system of planarians, which includes genes related to the CNS, also exist in humans.[15] Like planarians, vertebrates have a distinct CNS and PNS, though more complex than those of planarians.

In arthropods, the ventral nerve cord, the subesophageal ganglia and the supraesophageal ganglia are usually seen as making up the CNS.

The CNS of chordates differs from that of other animals in being placed dorsally in the body, above the gut and notochord/spine.[16] The basic pattern of the CNS is highly conserved throughout the different species of vertebrates and during evolution. The major trend that can be observed is towards a progressive telencephalisation: the telencephalon of reptiles is only an appendix to the large olfactory bulb, while in mammals it makes up most of the volume of the CNS. In the human brain, the telencephalon covers most of the diencephalon and the mesencephalon. Indeed, the allometric study of brain size among different species shows a striking continuity from rats to whales, and allows us to complete the knowledge about the evolution of the CNS obtained through cranial endocasts.

Mammals which appear in the fossil record after the first fishes, amphibians, and reptiles are the only vertebrates to possess the evolutionarily recent, outermost part of the cerebral cortex known as the neocortex.[17] The neocortex of monotremes (the duck-billed platypus and several species of spiny anteaters) and of marsupials (such as kangaroos, koalas, opossums, wombats, and Tasmanian devils) lack the convolutions gyri and sulci found in the neocortex of most placental mammals (eutherians).[18] Within placental mammals, the size and complexity of the neocortex increased over time. The area of the neocortex of mice is only about 1/100 that of monkeys, and that of monkeys is only about 1/10 that of humans.[17] In addition, rats lack convolutions in their neocortex (possibly also because rats are small mammals), whereas cats have a moderate degree of convolutions, and humans have quite extensive convolutions.[17] Extreme convolution of the neocortex is found in dolphins, possibly related to their complex echolocation.

There are many central nervous system diseases and conditions, including infections of the central nervous system such as encephalitis and poliomyelitis, early-onset neurological disorders including ADHD and autism, late-onset neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and essential tremor, autoimmune and inflammatory diseases such as multiple sclerosis and acute disseminated encephalomyelitis, genetic disorders such as Krabbe's disease and Huntington's disease, as well as amyotrophic lateral sclerosis and adrenoleukodystrophy. Lastly, cancers of the central nervous system can cause severe illness and, when malignant, can have very high mortality rates.

Specialty professional organizations recommend that neurological imaging of the brain be done only to answer a specific clinical question and not as routine screening.[19]

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Spinal Cord Stem Cells Comments Off on Central nervous system – Wikipedia | January 11th, 2017

Pia mater ( or [1]), often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. Pia mater is medieval Latin meaning "tender mother".[1] The other two meningeal membranes are the dura mater and the arachnoid mater. Both the pia and arachnoid mater are derivatives of the neural crest while the dura is derived from embryonic mesoderm. Pia mater is a thin fibrous tissue that is impermeable to fluid. This allows the pia mater to enclose cerebrospinal fluid. By containing this fluid the pia mater works with the other meningeal layers to protect and cushion the brain. The pia mater allows blood vessels to pass through and nourish the brain. The perivascular space created between blood vessels and pia mater functions as a lymphatic system for the brain. When the pia mater becomes irritated and inflamed the result is meningitis.[2]

Pia mater is the thin, translucent, mesh-like meningeal envelope, spanning nearly the entire surface of the brain. It is absent only at the natural openings between the ventricles, the median aperture, and the lateral aperture. The pia firmly adheres to the surface of the brain and loosely connects to the arachnoid layer.[3] Because of this continuum, the layers are often referred to as the pia arachnoid or leptomeninges. A subarachnoid space exists between the arachnoid layer and the pia, into which the choroid plexus releases and maintains the cerebrospinal fluid (CSF). The subarachnoid space contains trabeculae, or fibrous filaments, that connect and bring stability to the two layers, allowing for the appropriate protection from and movement of the proteins, electrolytes, ions, and glucose contained within the CSF.[4] Romanian biologist Viorel Pais, through recent electron microscopy studies, has demonstrated for the first time in the specialty literature that pia mater is formed by cordocytes and blood vessels.

The thin membrane is composed of fibrous connective tissue, which is covered by a sheet of flat cells impermeable to fluid on its outer surface. A network of blood vessels travels to the brain and spinal cord by interlacing through the pia membrane. These capillaries are responsible for nourishing the brain.[5] This vascular membrane is held together by areolar tissue covered by mesothelial cells from the delicate strands of connective tissue called the arachnoid trabeculae. In the perivascular spaces, the pia mater begins as mesothelial lining on the outer surface, but the cells then fade to be replaced by neuroglia elements.[6]

Although the pia mater is primarily structurally similar throughout, it spans both the spinal cords neural tissue and runs down the fissures of the cerebral cortex in the brain. It is often broken down into two categories, the cranial pia mater (pia mater encephali) and the spinal pia mater (pia mater spinalis).

The section of the pia mater enveloping the brain is known as the cranial pia mater. It is anchored to the brain by the processes of astrocytes, which are glial cells responsible for many functions, including maintenance of the extracellular space. The cranial pia mater joins with the ependyma, which lines the cerebral ventricles to form choroid plexuses that produce cerebrospinal fluid. Together with the other meningeal layers, the function of the pia mater is to protect the central nervous system by containing the cerebrospinal fluid, which cushions the brain and spine.[4]

The cranial pia mater covers the surface of the brain. This layer goes in between the cerebral gyri and cerebellar laminae, folding inward to create the tela chorioidea of the third ventricle and the choroid plexuses of the lateral and third ventricles. At the level of the cerebellum, the pia mater membrane is more fragile due to the length of blood vessels as well as decreased connection to the cerebral cortex.[6]

The spinal pia mater closely follows and encloses the curves of the spinal cord, and is attached to it through a connection to the anterior fissure. The pia mater attaches to the dura mater through 21 pairs of denticulate ligaments that pass through the arachnoid mater and dura mater of the spinal cord. These denticular ligaments help to anchor the spinal cord and prevent side to side movement, providing stability.[7] The membrane in this area is much thicker than the cranial pia mater, due to the two-layer composition of the pia membrane. The outer layer, which is made up of mostly connective tissue, is responsible for this thickness. Between the two layers are spaces which exchange information with the subarachnoid cavity as well as blood vessels. At the point where the pia mater reaches the conus medullaris or medullary cone at the end of the spinal cord, the membrane extends as a thin filament called the filum terminale or terminal filum, contained within the lumbar cistern. This filament eventually blends with the dura mater and extends as far as the coccyx, or tailbone. It then fuses with the periosteum, a membrane found at the surface of all bones, and forms the coccygeal ligament. There it is called the central ligament and assists with movements of the trunk of the body.[6]

In conjunction with the other meningeal membranes, pia mater functions to cover and protect the central nervous system (CNS), to protect the blood vessels and enclose the venous sinuses near the CNS, to contain the cerebrospinal fluid (CSF) and to form partitions with the skull.[8] The CSF, pia mater, and other layers of the meninges work together as a protection device for the brain, with the CSF often referred to as the fourth layer of the meninges.

Cerebrospinal fluid is circulated through the ventricles, cisterns, and subarachnoid space within the brain and spinal cord. About 150mL of CSF is always in circulation, constantly being recycled through the daily production of nearly 500mL of fluid. The CSF is primarily secreted by the choroid plexus; however, about one-third of the CSF is secreted by pia mater and the other ventricular ependymal surfaces (the thin epithelial membrane lining the brain and spinal cord canal) and arachnoidal membranes. The CSF travels from the ventricles and cerebellum through three foramina in the brain, emptying into the cerebrum, and ending its cycle in the venous blood via structures like the arachnoid granulations. The pia spans every surface crevice of the brain other than the foramina to allow the circulation of CSF to continue.[9]

Pia mater allows for the formation of perivascular spaces that help serve as the brains lymphatic system. Blood vessels that penetrate the brain first pass across the surface and then go inwards toward the brain. This direction of flow leads to a layer of the pia mater being carried inwards and loosely adhering to the vessels, leading to the production of a space, namely a perivascular space, between the pia mater and each blood vessel. This is critical because the brain lacks a true lymphatic system. In the remainder of the body, small amounts of protein are able to leak from the parenchymal capillaries through the lymphatic system. In the brain, this ends up in the interstitial space. The protein portions are able to leave through the very permeable pia mater and enter the subarachnoid space in order to flow in the cerebrospinal fluid (CSF), eventually ending up in the cerebral veins. The pia mater serves to create these perivascular spaces to allow passage of certain material, such as fluids, proteins, and even extraneous particulate matter such as dead white blood cells from the blood stream to the CSF, and essentially the brain.[9]

A function of the pia mater is that of the bloodbrain barrier (BBB), which keeps the CSF and brain fluid separate from the blood, allowing limited sodium, chlorine, and potassium through, and absolutely no plasma proteins nor organic molecules. Nearby, the ventricles are lined with the ependyma membrane. The CSF is only kept separate through the pia mater. Due to the ependyma and pia maters high permeability, nearly anything entering the CSF is able to enter the brain interstitial fluid.[9] However, regulation of this permeability is achieved through the abundant amount of astrocyte foot processes which are responsible for connecting the capillaries and the pia mater in a way that helps limit the amount of free diffusion going into the CNS.[10] The permeability of the pia then serves to closely connect the interstitial brain fluid and the CSF and allow them to remain nearly homogenous in terms of composition.[9]

The function of the pia mater is more simply visualized through these ordinary occurrences. This last property is evident in cases of head injury. When the head comes into contact with another object, the brain is protected from the skull due to the similarity in density between these two fluids so that the brain does not simply smash through into the skull, but rather its movement is slowed and stopped by the viscous ability of this fluid. The contrast in permeability between the BBB and pia mater mentioned before is also useful in the application of medicine. Drugs that enter the blood stream can not penetrate and function in the brain, but instead must be administered into the cerebrospinal fluid.[9]

The pia mater also functions to deal with the deformation of the spinal cord under compression. Due to the high elastic modulus of the pia mater, it is able to provide a constraint on the surface of the spinal cord. This constraint stops the elongation of the spinal cord, as well as providing a high strain energy. This high strain energy is useful and responsible for the restoration of the spinal cord to its original shape following a period of decompression.[11]

Ventral root afferents are unmyelinated sensory axons located within the pia mater. These ventral root afferents relay sensory information from the pia mater and allow for the transmission of pain from disc herniation and other spinal injury.[12]

The significant increase in the size of the cerebral hemisphere through evolution has been made possible in part through the evolution of the vascular pia mater, which allows nutrient blood vessels to penetrate deep into the intertwined cerebral matter, providing the necessary nutrients in this larger neural mass. Throughout the course of life on earth, the nervous system of animals has continued to evolve to a more compact and increased organization of neurons and other nervous system cells. This process is most evident in vertebrates and especially mammals in which the increased size of the brain is generally condensed into a smaller space through the presence of sulci or fissures on the surface of the hemisphere divided into gyri allowing more superficies of the cortical grey matter to exist. The development of the meninges and the existence of a defined pia mater was first noted in the vertebrates, and has been more and more significant membrane in the brains of mammals with larger brains.[13]

Meningitis is the inflammation of the pia and arachnoid mater. This is often due to bacteria that have entered the subarachnoid space, but can also be caused by viruses, fungi, as well as non-infectious causes such as certain drugs. It is believed that bacterial meningitis is caused by bacteria that enter the central nervous system through the blood stream. The molecular tools these pathogens would require to cross the meningeal layers and the bloodbrain barrier are not yet well understood. Inside the subarachnoid, bacteria replicate and cause inflammation from released toxins such as hydrogen peroxide (H2O2) . These toxins have been found to damage the mitochondria and produce a large scale immune response. Headache and meningismus are often signs of inflammation relayed via trigeminal sensory nerve fibers within the pia mater. Disabling neuropsychological effects are seen in up to half of bacterial meningitis survivors. Research into how bacteria invade and enter the meningeal layers is the next step in prevention of the progression of meningitis.[14]

A tumor growing from the meninges is referred to as a meningioma. Most meningiomas grow from the arachnoid mater inward applying pressure on the pia mater and therefore the brain or spinal cord. While meningiomas make up 20% of primary brain tumors and 12% of spinal cord tumors, 90% of these tumors are benign. Meningiomas tend to grow slowly and therefore symptoms may arise years after initial tumor formation. The symptoms often include headaches and seizures due to the force the tumor creates on sensory receptors. The treatments available for these tumors include surgery and radiation.[15]

Median sagittal section of brain

Coronal section of inferior horn of lateral ventricle

Diagrammatic representation of a section across the top of the skull, showing the membranes of the brain, etc.

Diagrammatic section of scalp

Ultrastructural diagram of the cerebral cortex (Viorel Pais, 2012)

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Pia mater - Wikipedia

Spinal Cord Stem Cells Comments Off on Pia mater – Wikipedia | January 8th, 2017

It may sound like science fiction, but the research of Stephanie Willerth of the University of Victoria is proving to be anything but. A patients adult cells will be reprogrammed back into their stem cell state.....

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Septic shock is the most severe form of infection seen in intensive care units (ICUs), a sneaky and unpredictable condition according to the Ottawa Health Research Institutes Dr. Lauralyn McIntyre...

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Its been 12 years since Canada passed legislation governing research on human embryos. As it stands, the legislation has not kept pace with the science... ...

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Umbilical cord blood can be a promising source of hematopoietic stem cells (HSCs), used in treating blood diseases...

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Liver transplants save lives, plain and simple. But they also sentence recipients to a lifetime of immune-suppressive drugs, to prevent the body from rejecting the foreign addition....

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Its an exciting time for the Stem Cell Network! We have been very busy over the past few months ensuring that we are able to deliver on our mandate and see research funding and training opportunities provided for...

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Spinal Cord Stem Cells Comments Off on Stem Cell Network | January 7th, 2017

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Neurology - Spinal Cord Introduction - YouTube

Spinal Cord Stem Cells Comments Off on Neurology – Spinal Cord Introduction – YouTube | January 6th, 2017

Clinical trials using neural stem cells

Neural stem cells (mouse)

StemCell Inc In December 2010 the Swiss regulatory agency for therapeutic products gave the go-ahead for aStemCell, Inc.-SponsoredPhase I/II clinical trial on chronic spinal cord injuryat the Balgrist University Hospital in Zurich (Switzerland). This trial had been inspired by the preclinical evidence of direct oligodendrocyte cell replacement through human neural stem cell (NSC) transplants in early chronic SCI in a particular mouse model. The trial uses a type of stem cell derived from human brain tissue and can make any of the three major kinds of neural cells found in the central nervous system. A single donor can provide eough cells for several transplanted patients). A single dose (20 x 106cells) of HuCNS-SC is directly implanted through multiple injections into thethoracicspinal cord of patients with chronic thoracic (T2T11) SCI, and immune suppression administered for 9 months after transplantation. This trial had enrolled patients 312 months after complete and incomplete cord injuries. The estimated completion date of this study is March 2016 (clinicaltrials.govidentifier no. NCT01321333). Interim analysis of clinical data to May 2014, presented at the Annual Meeting of the American Spinal Injury Association in San Antonio, Texas has shown that the significant post-transplant gains in sensory function first reported in two patients have now been observed in two additional patients.

The next group of patients currently being recruited in North America (University of Calgary) as well as in Switzerland has included some with incomplete injuries (ie some retained sensory or motor function) (clinicaltrials.govidentifier no. NCT01725880).

Earlier last year, the same company completed enrollment in multicentre open-label Phase I/II clinical titled "Study of Human Central Nervous System (CNS) Stem Cell Transplantation in Cervical Spinal Cord Injury" (Pathway Study website;clinicaltrials.govidentifier no. NCT02163876). The Pathway Study is the first clinical study designed to evaluate both the safetyandefficacy of transplanting stem cells. A total of 52 patients with traumatic injury to the cervical spinal cord are enrolled in the trial. The trial will be conducted as a randomized, controlled, single blind study and efficacy will be primarily measured by assessing motor function according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). The primary efficacy outcome will focus on change in upper extremity strength as measured in the hands, arms, and shoulders. The trial will follow the patients for one year from the time of enrollment.

The hope is that when transplanted into the injured spinal cord, these cells may re-establish some of the circuitries important for the network of nerves that carry information around the body.

Neuralstem Neuralstembegan surgeries in a Phase I safety trial of its NSI-566 neural stem cells for chronic spinal cord injury (cSCI) at the University of California, San Diego School of Medicine, with support from the UC San Diego Sanford Stem Cell Clinical Center, in September 2014 (clinicaltrials.govidentifier no. NCT01772810). The FDA amended the Phase I trial protocol to include a total of four patients, as the safety of the same cells and a similar procedure were proven in Neuralstems NSI-566/ALS trials. The four cSCI patients, with thoracic spinal cord injuries (T2-T12), have an American Spinal Injury Association (AIS) grade A level of impairment one-to-two years post-injury. This means that they have no motor or sensory function in the relevant segments at or below the injury, and are considered to be completely paralysed.

All patients in the trial will receive six injections in, or around, the injury site, using the same cells and similar procedure as the companys Amyotrophic Lateral Sclerosis (ALS) trials (the first FDA-approved neural stem cell trial for the treatment of ALS). All patients will also receive physical therapy post-surgery to guide newly formed nerves to their proper connections and functionality. The patients will also receive immunosuppressive therapy, which will be for three months, as tolerated. The trial study period will end six months post-surgery of the last patient, with a one-year Phase I completion goal. An NSI-566/acute spinal cord injury Phase I/II trial is expected to commence in the first quarter of 2015 in Seoul, South Korea.

The Miami Project to Cure Paralysis The Miami Projectclinical researchers currently have several clinical trials and clinical studies available for people who have had a spinal cord injury; some are for acute injuries and some are for chronic injuries. The clinical trials are testing the safety and efficacy of different cellular, neuroprotective, reparative, or modulatory interventions. These include Phase I clinical trials with the patients own (peripheral nerve-derived) Schwann cells in bothsubacute thoracicandchronic cervical and thoracicSCIs and a multicenter Phase II clinical trial withHuCNS-SC in chronic cervical SCIs(as above). All these Miami Project cell therapy trials are recruiting patients (more info on clinicaltrials.gov).

Mesenchymal/stromal stem cellsare being investigated as possible treatments for spinal cord injuries. Clinical Trials (clinicaltrials.gov) identifies at present total of 9 trials tagged as MSC trials in spinal cord injuries. These include studies that investigate the safety and efficacy of MSCs derived from the patients own bone marrow (5), adipose tissue (fat) (3) or cord blood (1). MSCs are injected in a number of different ways in these trials - including directly into the spinal cord or the lesion itself, intravenously, or even just in the skin, in patients with chronic cervical to thoracic injuries showingASIA/ISCoS scoresbetween A (complete lack of motor and sensory function below the level of injury) and C (some muscle movement is spared below the level of injury, but 50 percent of the muscles below the level of injury cannot move against gravity).

The hope is that when transplanted into the injured spinal cord, these cells may provide tissue protective molecules/factors and help (indirectly from cell integration and differentiation) to re-establish some of the circuitries important for the network of nerves that carry information around the body.

California based biotech Geronhad a widely reported clinical trial under way for a treatment the first of its kind involving the injection of cells derived from human embryonic stem cells. The injected cells were precursors of oligodendrocytes, the cells that form the insulating myelin sheath around axons. Researchers hoped that these cells, once injected into the spinal cord, would mature and form a new coating on the nerve cells, restoring the ability of signals to cross the spinal cord injury site.

After treating four patients with these cells in a phase one (safety) trial, and reporting no serious adverse effects, Geron announced in November 2011 it was discontinuing its stem cell programme. The company said stem cells continue to hold great promise, but cited financial reasons for shifting focus to other areas of research.

Asterias Biotherapeutics Following up on the cellular technology initially developed by Geron, Asterias Biotherapeutics has developed a program that focuses on the development of a kind of nerve cell, oligodendrocyte progenitor cells (OPCs) for spinal cord injury. These cells, known as AST-OPC1, are produced from human embryonic stem (ES) cells.

In aPhase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million hES cell-derived OPCs at the spinal cord injury site 7-14 days post-injury. The subjects received low levels immunosuppression for the next 60 days. Delivery of OPCs was successful in all five subjects with no serious adverse events associated with the administration of the cells or the immunosuppressive regimen. In four of the five subjects, serial MRI scans suggested reduction of the volume of injury in the spinal cord

A second follow up (dose escalation)Phase I/II trialwith AST-OPC1 in acute (14-30 days after injury) sensorimotor complete cervical spinal cord injuries (SCI) is currently recruiting participants.

The hope is that when acutely transplanted into the injured spinal cord, OPCs may remyelinate and restore lost functions.

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Spinal cord injuries: how could stem cells help ...

Spinal Cord Stem Cells Comments Off on Spinal cord injuries: how could stem cells help … | December 25th, 2016

December 13, 2016 - Experimental implant shows promise for restoring voluntary movement after spinal cord injury

UCLA scientists test electrical stimulation that bypasses injury; technique boosts patients finger control, grip strength up to 300 percent A spinal stimulator being tested by doctors at Ronald Reagan UCLA Medical Center is showing promise in restoring hand strength and movement to a California man who broke his neck in a dirt bike accident five Continue Reading

Researchers have developed a urine test revealing the presence of a neurotoxin that likely worsens the severity and pain of spinal cord injuries, suggesting a new tool to treat the injuries. The neurotoxin, called acrolein, is produced within the body after nerve cells are damaged, increasing pain and triggering a cascade of biochemical events thought Continue Reading

We are trying to improve someones quality of life. If someone can breathe without a ventilator, then youve increased their independence, and that, to me, is a huge success. Michael Lane, PhD Walking is not the top priority for many patients who have suffered from cervical spinal cord injuries, according to Michael Lane, PhD, an Continue Reading

Scientists have developed a robotic interface which could help to restore fine hand movements in paraplegics. By combining an electrode cap with an exoskeleton worn over the fingers, the device translates brain signals to hand movements. The approach could provide paraplegic patients with the fine motor control needed to carry out everyday tasks such as Continue Reading

In the course of three years, Taylor Graham has accomplished many things: Survived a motorcycle accident, adjusted to a spinal cord injury and a new life in a wheelchair, picked up the sport of wheelchair tennis, graduated from Southeast Community College, and even got married. So what could possibly be next? We have a goal Continue Reading

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Spinal Cord Injury Zone!

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury Zone! | December 25th, 2016

Spinal cord injuries result from damage to the vertebrae, ligaments or disks of the spinal column or to the spinal cord itself.

A traumatic spinal cord injury may stem from a sudden, traumatic blow to your spine that fractures, dislocates, crushes, or compresses one or more of your vertebrae. It also may result from a gunshot or knife wound that penetrates and cuts your spinal cord.

Additional damage usually occurs over days or weeks because of bleeding, swelling, inflammation and fluid accumulation in and around your spinal cord.

A nontraumatic spinal cord injury may be caused by arthritis, cancer, inflammation, infections or disk degeneration of the spine.

The central nervous system comprises the brain and spinal cord. The spinal cord, made of soft tissue and surrounded by bones (vertebrae), extends downward from the base of your brain and is made up of nerve cells and groups of nerves called tracts, which go to different parts of your body.

The lower end of your spinal cord stops a little above your waist in the region called the conus medullaris. Below this region is a group of nerve roots called the cauda equina.

Tracts in your spinal cord carry messages between the brain and the rest of the body. Motor tracts carry signals from the brain to control muscle movement. Sensory tracts carry signals from body parts to the brain relating to heat, cold, pressure, pain and the position of your limbs.

Whether the cause is traumatic or nontraumatic, the damage affects the nerve fibers passing through the injured area and may impair part or all of your corresponding muscles and nerves below the injury site.

A chest (thoracic) or lower back (lumbar) injury can affect your torso, legs, bowel and bladder control, and sexual function. In addition, a neck (cervical) injury affects movements of your arms and, possibly, your ability to breathe.

The most common causes of spinal cord injuries in the United States are:

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Spinal cord injury Causes - Mayo Clinic

Spinal Cord Stem Cells Comments Off on Spinal cord injury Causes – Mayo Clinic | November 27th, 2016

The spine has different sections. The level of paralysis depends on the location of the injury.The spinal cord is made up of millions of nerve cells that send projections up and down the cord and out into other parts of the body. The information that allows us to sit, run, go to the toilet and breathe travels along these projections, called nerves.

When the spinal cord is injured, the initial trauma causes cell damage and destruction, and triggersa cascade of eventsthat spread around the injury site affecting a number of different types of cells. Axons are crushed and torn, and oligodendrocytes, the nerve cells that make up the insulating myelin sheath around axons, begin to die. Exposed axons degenerate, the connection between neurons is disrupted and the flow of information between the brain and the spinal cord is blocked.

The body cannot replace cells lost when the spinal cord is injured, and its function becomes impaired permanently. Patients may end up with severe movement and sensation disabilities. They will generally be paralyzed and without sensation from the level of the injury downwards.

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What happens when the spinal cord is injured? | Europe's ...

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the original, translation-focused global meeting of stakeholders

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Regenerative medicine and stem cell research are presenting possibilities that were unimaginable 15 years ago. Bernard Siegel, Founder of the World Stem Cell Summit, discusses its position at the heart of this community, bringing together

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(December 5, 2012 -- West Palm Beach, Florida) The winners of the World Stem Cell Summit Poster Prize were announced this morning by Alan Jakimo, Senior Counsel, Sidley Austin.The World Stem Cell Summit Poster Forum

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World Stem Cell Summit

Spinal Cord Stem Cells Comments Off on World Stem Cell Summit | November 21st, 2016

Spinal cord injury (SCI) causes the irreversible loss of spinal cord parenchyma including astroglia, oligodendroglia and neurons. In particular, severe injuries can lead to an almost complete neural cell loss at the lesion site and structural and functional recovery might only be accomplished by appropriate cell and tissue replacement. Stem cells have the capacity to differentiate into all relevant neural cell types necessary to replace degenerated spinal cord tissue and can now be obtained from virtually any stage of development. Within the last two decades, many in vivo studies in small animal models of SCI have demonstrated that stem cell transplantation can promote morphological and, in some cases, functional recovery via various mechanisms including remyelination, axon growth and regeneration, or neuronal replacement. However, only two well-documented neural-stem-cell-based transplantation strategies have moved to phase I clinical trials to date. This review aims to provide an overview about the current status of preclinical and clinical neural stem cell transplantation and discusses future perspectives in the field.

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Neural Stem Cells for Spinal Cord Repair

Spinal Cord Stem Cells Comments Off on Neural Stem Cells for Spinal Cord Repair | November 2nd, 2016

This article is about the medical therapy. For the cell type, see Stem cell.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition.

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions.

Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. This controversy is often related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

For over 30 years, bone marrow has been used to treat cancer patients with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced.[1][2][3] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment. The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, however, leading to graft vs host disease, the most serious side effect of this treatment.[4]

Another stem-cell therapy called Prochymal, was conditionally approved in Canada in 2012 for the management of acute graft-vs-host disease in children who are unresponsive to steroids.[5] It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from the bone marrow of adult donors. MSCs are purified from the marrow, cultured and packaged, with up to 10,000 doses derived from a single donor. The doses are stored frozen until needed.[6]

The FDA has approved five hematopoietic stem-cell products derived from umbilical cord blood, for the treatment of blood and immunological diseases.[7]

In 2014, the European Medicines Agency recommended approval of Holoclar, a treatment involving stem cells, for use in the European Union. Holoclar is used for people with severe limbal stem cell deficiency due to burns in the eye.[8]

In March 2016 GlaxoSmithKline's Strimvelis (GSK2696273) therapy for the treatment ADA-SCID was recommended for EU approval.[9]

Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in an effort to make medications.[10]

Research has been conducted on the effects of stem cells on animal models of brain degeneration, such as in Parkinson's, Amyotrophic lateral sclerosis, and Alzheimer's disease.[11][12][13] There have been preliminary studies related to multiple sclerosis.[14][15]

Healthy adult brains contain neural stem cells which divide to maintain general stem-cell numbers, or become progenitor cells. In healthy adult laboratory animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Pharmacological activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in adult rat models of neurological disorder.[16][17][18]

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. A small clinical trial was underway in Scotland in 2013, in which stem cells were injected into the brains of stroke patients.[19]

Clinical and animal studies have been conducted into the use of stem cells in cases of spinal cord injury.[20][21][22]

The pioneering work[23] by Bodo-Eckehard Strauer has now been discredited by the identification of hundreds of factual contradictions.[24] Among several clinical trials that have reported that adult stem-cell therapy is safe and effective, powerful effects have been reported from only a few laboratories, but this has covered old[25] and recent[26] infarcts as well as heart failure not arising from myocardial infarction.[27] While initial animal studies demonstrated remarkable therapeutic effects,[28][29] later clinical trials achieved only modest, though statistically significant, improvements.[30][31] Possible reasons for this discrepancy are patient age,[32] timing of treatment[33] and the recent occurrence of a myocardial infarction.[34] It appears that these obstacles may be overcome by additional treatments which increase the effectiveness of the treatment[35] or by optimizing the methodology although these too can be controversial. Current studies vary greatly in cell-procuring techniques, cell types, cell-administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed.

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone-marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells.[36] Adult stem cell therapy for treating heart disease was commercially available in at least five continents as of 2007.[citation needed]

Possible mechanisms of recovery include:[11]

It may be possible to have adult bone-marrow cells differentiate into heart muscle cells.[11]

The first successful integration of human embryonic stem cell derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.[37]

In 2013 the pioneering reports of powerful beneficial effects of autologous bone marrow stem cells on ventricular function were found to contain "hundreds" of discrepancies.[38] Critics report that of 48 reports there seemed to be just five underlying trials, and that in many cases whether they were randomized or merely observational accepter-versus-rejecter, was contradictory between reports of the same trial. One pair of reports of identical baseline characteristics and final results, was presented in two publications as, respectively, a 578 patient randomized trial and as a 391 patient observational study. Other reports required (impossible) negative standard deviations in subsets of patients, or contained fractional patients, negative NYHA classes. Overall there were many more patients published as having receiving stem cells in trials, than the number of stem cells processed in the hospital's laboratory during that time. A university investigation, closed in 2012 without reporting, was reopened in July 2013.[39]

One of the most promising benefits of stem cell therapy is the potential for cardiac tissue regeneration to reverse the tissue loss underlying the development of heart failure after cardiac injury.[40]

Initially, the observed improvements were attributed to a transdifferentiation of BM-MSCs into cardiomyocyte-like cells.[28] Given the apparent inadequacy of unmodified stem cells for heart tissue regeneration, a more promising modern technique involves treating these cells to create cardiac progenitor cells before implantation to the injured area.[41]

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are diagnosed and classified via a subspecialty of pathology known as hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red-blood-cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[42] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[43] and were able to grow bioengineered teeth stand-alone in the laboratory. Researchers are confident that the tooth regeneration technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to be grown in a time over three weeks.[44] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[45][46]

Research is ongoing in different fields, alligators which are polyphyodonts grow up to 50 times a successional tooth (a small replacement tooth) under each mature functional tooth for replacement once a year.[47]

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[48]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[49] The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[50]

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[51]

In 2014, researchers demonstrated that stem cells collected as biopsies from donor human corneas can prevent scar formation without provoking a rejection response in mice with corneal damage.[52]

In January 2012, The Lancet published a paper by Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.[53]

In June 2015, the Stem Cell Ophthalmology Treatment Study (SCOTS), the largest adult stem cell study in ophthalmology ( http://www.clinicaltrials.gov NCT # 01920867) published initial results on a patient with optic nerve disease who improved from 20/2000 to 20/40 following treatment with bone marrow derived stem cells.[54]

Diabetes patients lose the function of insulin-producing beta cells within the pancreas.[55] In recent experiments, scientists have been able to coax embryonic stem cell to turn into beta cells in the lab. In theory if the beta cell is transplanted successfully, they will be able to replace malfunctioning ones in a diabetic patient.[56]

Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:[11]

Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.[57][58] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4-year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[59]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[60]

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[61] A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[61] Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.[61]

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[62]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[63] It could potentially treat azoospermia.

In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes.[64] These cells have the potential to treat infertility.

Destruction of the immune system by the HIV is driven by the loss of CD4+ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the primary targets of productive HIV infection.[65] Recently scientists have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC).[66]

On 23 January 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions".[67] In 2013 biotechnology and regenerative medicine company BioTime (NYSEMKT:BTX) acquired Geron's stem cell assets in a stock transaction, with the aim of restarting the clinical trial.[68]

Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth(fresh), so cryopreserved MSCs should be brought back into log phase of cell growth in invitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[69]

Research currently conducted on horses, dogs, and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans.[70][71][72][73] While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[74] Companion animals can serve as clinically relevant models that closely mimic human disease.[75][76]

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections.[110] There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

Stem-cell research and treatment was practiced in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem-cell therapy for conditions beyond those approved of in Western countries. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures.[111]

Since 2008 many universities, centers and doctors tried a diversity of methods; in Lebanon proliferation for stem cell therapy, in-vivo and in-vitro techniques were used, Thus this country is considered the launching place of the Regentime[112] procedure. http://www.researchgate.net/publication/281712114_Treatment_of_Long_Standing_Multiple_Sclerosis_with_Regentime_Stem_Cell_Technique The regenerative medicine also took place in Jordan and Egypt.[citation needed]

Stem-cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. Authorized centers are found in Tijuana, Guadalajara and Cancun. Currently undergoing the approval process is Los Cabos. This permit allows the use of stem cell.[citation needed]

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.[113]

As of 2013, Thailand still considers Hematopoietic stem cell transplants as experimental. Kampon Sriwatanakul began with a clinical trial in October 2013 with 20 patients. 10 are going to receive stem-cell therapy for Type-2 diabetes and the other 10 will receive stem-cell therapy for emphysema. Chotinantakul's research is on Hematopoietic cells and their role for the hematopoietic system function in homeostasis and immune response.[114]

Today, Ukraine is permitted to perform clinical trials of stem-cell treatments (Order of the MH of Ukraine 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

Other countries where doctors did stem cells research, trials, manipulation, storage, therapy: Brazil, Cyprus, Germany, Italy, Israel, Japan, Pakistan, Philippines, Russia, Switzerland, Turkey, United Kingdom, India, and many others.

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Stem-cell therapy - Wikipedia

Spinal Cord Stem Cells Comments Off on Stem-cell therapy – Wikipedia | November 2nd, 2016

The transplantation of neural stem/progenitor cells (NPCs) is a promising therapeutic strategy for spinal cord injury (SCI). However, to date NPC transplantation has exhibited only limited success in the treatment of chronic SCI. Here, we show that chondroitin sulfate proteoglycans (CSPGs) in the glial scar around the site of chronic SCI negatively influence the long-term survival and integration of transplanted NPCs and their therapeutic potential for promoting functional repair and plasticity. We targeted CSPGs in the chronically injured spinal cord by sustained infusion of chondroitinase ABC (ChABC). One week later, the same rats were treated with transplants of NPCs and transient infusion of growth factors, EGF, bFGF, and PDGF-AA. We demonstrate that perturbing CSPGs dramatically optimizes NPC transplantation in chronic SCI. Engrafted NPCs successfully integrate and extensively migrate within the host spinal cord and principally differentiate into oligodendrocytes. Furthermore, this combined strategy promoted the axonal integrity and plasticity of the corticospinal tract and enhanced the plasticity of descending serotonergic pathways. These neuroanatomical changes were also associated with significantly improved neurobehavioral recovery after chronic SCI. Importantly, this strategy did not enhance the aberrant synaptic connectivity of pain afferents, nor did it exacerbate posttraumatic neuropathic pain. For the first time, we demonstrate key biological and functional benefits for the combined use of ChABC, growth factors, and NPCs to repair the chronically injured spinal cord. These findings could potentially bring us closer to the application of NPCs for patients suffering from chronic SCI or other conditions characterized by the formation of a glial scar.

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Synergistic effects of transplanted adult neural stem ...

Spinal Cord Stem Cells Comments Off on Synergistic effects of transplanted adult neural stem … | September 27th, 2016

GETTY

They suffer many complications in addition to paralysis and numbness and some of these problems are caused by a lack of the neurotransmitter GABA in the injured spinal cord.

A new University of California, San Francisco study in mice found human embryonic stem cells reduced two of the most severe side effects - incontinence and pain sensitivity.

Co-first author Assistant Professor Dr Cory Nicholas said: Chronic pain and bladder dysfunction remain significant quality-of-life issues for many people with spinal cord injuries.

Inhibitory cell-based neuro-therapy is a new approach and has shown promise to date in early animal studies, warranting further development."

The stem cell treatment differentiated into medial ganglionic eminence (MGE)-like cells, which produce GABA (gamma-Aminobutyric acid), an inhibitory neurotransmitter that is found throughout the central nervous system.

Our hope is that this treatment would last a long time, or maybe even be permanent

Dr Thomas Fandel

It plays an important role in reducing the excitability of neurons by binding to receptors that act on synapses.

Neuropathic pain and bladder dysfunction are at least in part attributed to overactive spinal cord circuits.

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Senior author Professor Dr Arnold Kriegstein said: We reasoned if we could take inhibitory neurons and directly place them into the spinal cord in the regions that are overactive, they might integrate into those circuits and suppress the activity.

In the study researchers used GABAergic inhibitory neuron precursors called MGE-like cells that were derived from human embryonic stem cells.

The neural precursor cells were placed into the spinal cords of mice two weeks after injury had been induced, where they could differentiate into GABA-producing neuron subtypes and form synaptic connections.

Co-author Dr Thomas Fandel, a research specialist at UCSF added: Rather than implanting these cells into the site of injury, at the mid-thoracic level, we injected them in the lumbosacral region, where the circuits are known to be overactive.

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Six months later we could see broad dispersion of the cells in that area. They were integrated into the spinal cord.

Tests showed the mice were not incontinent and had significantly reduced pain sensitivities.

Current treatments for neuropathic pain in people with spinal cord injuries most often involve opioids and other pain medications, as well as certain antidepressants, which have many side effects and tend to have limited efficacy.

Treatments for bladder dysfunction are often anticholinergics, but these drugs have side effects like dizziness and dry mouth.

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Botox may help with bladder spasms, but the benefits tend to be transient.

Dr Fandel added: The current approaches for treatment are not very effective and clearly more options are needed.

Our hope is that this treatment would last a long time, or maybe even be permanent.

The study was published in the journal Cell Stem Cell.

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Human stem cells could provide relief for spinal cord ...

Spinal Cord Stem Cells Comments Off on Human stem cells could provide relief for spinal cord … | September 26th, 2016

SAN FRANCISCO Researchers have successfully transplanted healthy human cells into mice with spinal cord injuries, bringing the world one step closer to easing the chronic pain and incontinence suffered by people with paralysis.

The research team did not focus on restoring the rodents ability to walk; rather, it helped remedy these two other debilitating side effects of spinal cord injury.

If successful in humans, thefindingscould someday ease the lives of those with these distressing conditions, said Dr. Arnold Kriegstein, co-senior author of the study and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC San Francisco. The research was published in Thursdays issue of the journal Cell Stem Cell.

This is a very important step, Kriegstein said. The treated animals improved in pain relief and bladder function.The research offers the promising potential of using a new therapeutic approach cell therapy to repair damaged neural tissue, showing that new cells can be integrated into an injured spinal cord.

A similar approach also has helped mice with epilepsy and Parkinsons disease.

More than aquarter of a million Americans live with spinal cord injuries, and 17,000 new cases occur each year, according to the National Spinal Cord Injury Statistical Center. More than half of those people go on to develop chronic pain in their limbs, called neuropathy. And nearly all develop bladder problems, which can result in kidney damage.

The spinal cord is the major highway for nerve cells to relay information between the brain and the rest of the body. When the spinal cord is injured, tears and inflammation harm surrounding cells.

The field has been very focused on restoring patients ability to walk, perhaps because thats often their most visible impairment, study co-authorLinda Noble-Haeusslein, a professor of physical therapy and rehabilitation at UCSF, said in a statement.

But a recent study showing that patients complained of pain and loss of bladder control more than paralysis suggested that we had really missed the boat as a field, she said. It caused us to dramatically shift what we do in the lab.

The cells used in the study, called neurons, were grown from human embryonic stem cells the bodys building blocks, capable of generating more than1,000 different types of adult cells.

They arent just any garden-variety neuron. These cells have the ability to inhibit, rather than excite, the neural network of the spine. Thats important because the pain and loss of bladder control are believed to be caused by overactivated neural circuits.

The healthy body keeps this excitable circuitry under control.But inflammation caused by a spinal cord injury causes a loss of this control.

The UCSF team grew the replacement cells in a South San Francisco biotech lab ofNeurona Therapeutics, founded by study co-authorCory Nicholasand Kriegstein, UCSFprofessor of developmental and stem cell biology. The company hopes to mass-produce these cells for use in future clinical trials.

They injected the young human cells into the spines of mice about two weeks afterinjury. They targeted the thoracic region about halfway up the spinal cord because thats a common site of injury for humans.But they were careful not to inject the young cells directly into the injured areas because that is a toxic place full of inflammation.

Remarkably, over the next six months the human cells matured, migrated toward the site of the injury and made connections with the spinal cords of the mice.

Compared to untreated mice, the treated rodents showed significantly less hypersensitivity to touch and painful stimuli and reduced abnormal scratching. Treated mice also had improved bladder function and produced more normal, voluntary patterns of urination in their cages.

A different research team is focusing on a fix for paralysis. This necessitatesa different strategy, requiring treatment with stem cell-derived neurons whose job it is to conduct electrical impulses down the spine. And these cells may face a more daunting environment if injected directly into injured areas.

The first trial by Geron Corp. stalled in late 2011, mostly because of financial concerns. But a Fremont-based biotech company calledAsterias Biotherapeutics, a subsidiary of BioTime, bought Gerons intellectual property and is continuing the research. It recently received approval fromthe U.S. Food and Drug Administration for a safety and early trial of the cells for treating spinal cord injury.

Meanwhile, the UCSF team is working to replicate their findings of improved bladder control and chronic pain. And they seek to learn the best time to inject the cells. Funders for the research included the National Institutes of Health and the California Institute of Regenerative Medicine.

The team is hoping to scale up their production of their specialized cells with the goal of entering human trials, after proving to the FDA that their effort is safe.

We are eager to move in that direction as quickly as we can, Kriegstein said.

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spinal cord injury, embryonic stem cells, paralysis, pain ...

Spinal Cord Stem Cells Comments Off on spinal cord injury, embryonic stem cells, paralysis, pain … | September 26th, 2016

Engrafted NSPCs Form Presynaptic Connectivity with Spared Host Neurons after SCI (A) The gene expression levels of pan-presynaptic markers in engrafted NSPCs at 6weeks after transplantation, as determined by qRT-PCR, are shown (n= 8 mice per group). (B) Triple-staining for GFP (green), HU (blue), and the presynaptic marker BASSOON (red) at 6weeks after transplantation. The images showed that the engrafted NSPCs expressed BASSOON-positive synaptic boutons (arrowhead) in their axon terminals, which surrounded HU-positive host neurons. The right image is a magnification of the boxed area in the left image. (C) Quantification of the GFP/BASSOON-positive synaptic boutons in engrafted NSPCs is shown (n= 60 neurons; six mice per group). (D and E) The gene expression levels of inhibitory presynaptic markers (Vgat, Gad65, and Gad67) and excitatory presynaptic markers(Vglut1 and Vglut2) in engrafted NSPCs at 6weeks after transplantation, as determined by qRT-PCR, are shown (n= 8 mice per group). (F) Triple-staining for GFP (green), HU (blue), and the excitatory presynaptic marker VGLUT2 (red) at 6weeks after transplantation. The images showed that the GFP/VGLUT2-positive excitatory synaptic boutons (arrowhead) contacted HU-positive host neurons. The right image is a magnification of the boxed area in the left image. (G) Quantification of the GFP/VGLUT2-positive synaptic boutons in engrafted NSPCs is shown (n= 60 neurons; six mice per group). p< 0.05, p< 0.0001, Wilcoxon rank-sum test (A, C, D, E, and G). The data are presented as the means SEM. Scale bars, 20m (B and F) and 2m (insets).

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Engrafted Neural Stem/Progenitor Cells Promote Functional ...

Spinal Cord Stem Cells Comments Off on Engrafted Neural Stem/Progenitor Cells Promote Functional … | September 7th, 2016

3.1 Introduction

Figure 3.1 Schematic dorsal and lateral view of the spinal cord and four cross sections from cervical, thoracic, lumbar and sacral levels, respectively.

The spinal cord is the most important structure between the body and the brain. The spinal cord extends from the foramen magnum where it is continuous with the medulla to the level of the first or second lumbar vertebrae. It is a vital link between the brain and the body, and from the body to the brain. The spinal cord is 40 to 50 cm long and 1 cm to 1.5 cm in diameter. Two consecutive rows of nerve roots emerge on each of its sides. These nerve roots join distally to form 31 pairs of spinal nerves. The spinal cord is a cylindrical structure of nervous tissue composed of white and gray matter, is uniformly organized and is divided into four regions: cervical (C), thoracic (T), lumbar (L) and sacral (S), (Figure 3.1), each of which is comprised of several segments. The spinal nerve contains motor and sensory nerve fibers to and from all parts of the body. Each spinal cord segment innervates a dermatome (see below and Figure 3.5).

3.2 General Features

Although the spinal cord constitutes only about 2% of the central nervous system (CNS), its functions are vital. Knowledge of spinal cord functional anatomy makes it possible to diagnose the nature and location of cord damage and many cord diseases.

3.3 Segmental and Longitudinal Organization

The spinal cord is divided into four different regions: the cervical, thoracic, lumbar and sacral regions (Figure 3.1). The different cord regions can be visually distinguished from one another. Two enlargements of the spinal cord can be visualized: The cervical enlargement, which extends between C3 to T1; and the lumbar enlargements which extends between L1 to S2 (Figure 3.1).

The cord is segmentally organized. There are 31 segments, defined by 31 pairs of nerves exiting the cord. These nerves are divided into 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal nerve (Figure 3.2). Dorsal and ventral roots enter and leave the vertebral column respectively through intervertebral foramen at the vertebral segments corresponding to the spinal segment.

Figure 3.2 Drawing of the 8, 12, 5, 5 and 1 cervical, thoracic, lumbar, sacral and coccygeal spinal nerves and their exit from the vertebrate, respectively.

The cord is sheathed in the same three meninges as is the brain: the pia, arachnoid and dura. The dura is the tough outer sheath, the arachnoid lies beneath it, and the pia closely adheres to the surface of the cord (Figure 3.3). The spinal cord is attached to the dura by a series of lateral denticulate ligaments emanating from the pial folds.

Figure 3.3 The three spinal cord meninges. The denticulate ligament, the dorsal root ganglion (A), and an enlarged drawing of the meninges (B).

During the initial third month of embryonic development, the spinal cord extends the entire length of the vertebral canal and both grow at about the same rate. As development continues, the body and the vertebral column continue to grow at a much greater rate than the spinal cord proper. This results in displacement of the lower parts of the spinal cord with relation to the vertebrae column. The outcome of this uneven growth is that the adult spinal cord extends to the level of the first or second lumbar vertebrae, and the nerves grow to exit through the same intervertebral foramina as they did during embryonic development. This growth of the nerve roots occurring within the vertebral canal, results in the lumbar, sacral, and coccygeal roots extending to their appropriate vertebral levels (Figure 3.2).

All spinal nerves, except the first, exit below their corresponding vertebrae. In the cervical segments, there are 7 cervical vertebrae and 8 cervical nerves (Figure 3.2). C1-C7 nerves exit above their vertebrae whereas the C8 nerve exits below the C7 vertebra. It leaves between the C7 vertebra and the first thoracic vertebra. Therefore, each subsequent nerve leaves the cord below the corresponding vertebra. In the thoracic and upper lumbar regions, the difference between the vertebrae and cord level is three segments. Therefore, the root filaments of spinal cord segments have to travel longer distances to reach the corresponding intervertebral foramen from which the spinal nerves emerge. The lumbosacral roots are known as the cauda equina (Figure 3.2).

Each spinal nerve is composed of nerve fibers that are related to the region of the muscles and skin that develops from one body somite (segment). A spinal segment is defined by dorsal roots entering and ventral roots exiting the cord, (i.e., a spinal cord section that gives rise to one spinal nerve is considered as a segment.) (Figure 3.4).

Figure 3.4 (A) Drawing of the spinal cord with its spinal roots. (B) Drawing of the spinal vertebrate. (C) Section of the spinal cord, its meninges and the dorsal and ventral roots of three segments.

A dermatome is an area of skin supplied by peripheral nerve fibers originating from a single dorsal root ganglion. If a nerve is cut, one loses sensation from that dermatome. Because each segment of the cord innervates a different region of the body, dermatomes can be precisely mapped on the body surface, and loss of sensation in a dermatome can indicate the exact level of spinal cord damage in clinical assessment of injury (Figure 3.5). It is important to consider that there is some overlap between neighboring dermatomes. Because sensory information from the body is relayed to the CNS through the dorsal roots, the axons originating from dorsal root ganglion cells are classified as primary sensory afferents, and the dorsal root's neurons are the first order (1) sensory neuron. Most axons in the ventral roots arise from motor neurons in the ventral horn of the spinal cord and innervate skeletal muscle. Others arise from the lateral horn and synapse on autonomic ganglia that innervate visceral organs. The ventral root axons join with the peripheral processes of the dorsal root ganglion cells to form mixed afferent and efferent spinal nerves, which merge to form peripheral nerves. Knowledge of the segmental innervation of the cutaneous area and the muscles is essential to diagnose the site of an injury.

Figure 3.5 Innervation arising from single dorsal root ganglion supplied specific skin area (a dermatome). The numbers refer to the spinal segments by which each nerve is named C = cervical; T = thoracic; L = lumbar; S = sacral spinal cord segments (dermatome).

3.4 Internal Structure of the Spinal Cord

A transverse section of the adult spinal cord shows white matter in the periphery, gray matter inside, and a tiny central canal filled with CSF at its center. Surrounding the canal is a single layer of cells, the ependymal layer. Surrounding the ependymal layer is the gray matter a region containing cell bodies shaped like the letter H or a butterfly. The two wings of the butterfly are connected across the midline by the dorsal gray commissure and below the white commissure (Figure 3.6). The shape and size of the gray matter varies according to spinal cord level. At the lower levels, the ratio between gray matter and white matter is greater than in higher levels, mainly because lower levels contain less ascending and descending nerve fibers. (Figure 3.1 and Figure 3.6).

Figure 3.6 Spinal cord section showing the white and the gray matter in four spinal cord levels.

The gray matter mainly contains the cell bodies of neurons and glia and is divided into four main columns: dorsal horn, intermediate column, lateral horn and ventral horn column. (Figure 3.6).

The dorsal horn is found at all spinal cord levels and is comprised of sensory nuclei that receive and process incoming somatosensory information. From there, ascending projections emerge to transmit the sensory information to the midbrain and diencephalon. The intermediate column and the lateral horn comprise autonomic neurons innervating visceral and pelvic organs. The ventral horn comprises motor neurons that innervate skeletal muscle.

At all the levels of the spinal cord, nerve cells in the gray substance are multipolar, varying much in their morphology. Many of them are Golgi type I and Golgi type II nerve cells. The axons of Golgi type I are long and pass out of the gray matter into the ventral spinal roots or the fiber tracts of the white matter. The axons and dendrites of the Golgi type II cells are largely confined to the neighboring neurons in the gray matter.

A more recent classification of neurons within the gray matter is based on function. These cells are located at all levels of the spinal cord and are grouped into three main categories: root cells, column or tract cells and propriospinal cells.

The root cells are situated in the ventral and lateral gray horns and vary greatly in size. The most prominent features of the root cells are large multipolar elements exceeding 25 m of their somata. The root cells contribute their axons to the ventral roots of the spinal nerves and are grouped into two major divisions: 1) somatic efferent root neurons, which innervate the skeletal musculature; and 2) the visceral efferent root neurons, also called preganglionic autonomic axons, which send their axons to various autonomic ganglia.

The column or tract cells and their processes are located mainly in the dorsal gray horn and are confined entirely within the CNS. The axons of the column cells form longitudinal ascending tracts that ascend in the white columns and terminate upon neurons located rostrally in the brain stem, cerebellum or diencephalon. Some column cells send their axons up and down the cord to terminate in gray matter close to their origin and are known as intersegmental association column cells. Other column cell axons terminate within the segment in which they originate and are called intrasegmental association column cells. Still other column cells send their axons across the midline to terminate in gray matter close to their origin and are called commissure association column cells.

The propriospinal cells are spinal interneurons whose axons do not leave the spinal cord proper. Propriospinal cells account for about 90% of spinal neurons. Some of these fibers also are found around the margin of the gray matter of the cord and are collectively called the fasciculus proprius or the propriospinal or the archispinothalamic tract.

3.5 Spinal Cord Nuclei and Laminae

Spinal neurons are organized into nuclei and laminae.

3.6 Nuclei

The prominent nuclear groups of cell columns within the spinal cord from dorsal to ventral are the marginal zone, substantia gelatinosa, nucleus proprius, dorsal nucleus of Clarke, intermediolateral nucleus and the lower motor neuron nuclei.

Figure 3.7 Spinal cord nuclei and laminae.

Marginal zone nucleus or posterior marginalis, is found at all spinal cord levels as a thin layer of column/tract cells (column cells) that caps the tip of the dorsal horn. The axons of its neurons contribute to the lateral spinothalamic tract which relays pain and temperature information to the diencephalon (Figure 3.7).

Substantia gelatinosa is found at all levels of the spinal cord. Located in the dorsal cap-like portion of the head of the dorsal horn, it relays pain, temperature and mechanical (light touch) information and consists mainly of column cells (intersegmental column cells). These column cells synapse in cell at Rexed layers IV to VII, whose axons contribute to the ventral (anterior) and lateral spinal thalamic tracts. The homologous substantia gelatinosa in the medulla is the spinal trigeminal nucleus.

Nucleus proprius is located below the substantia gelatinosa in the head and neck of the dorsal horn. This cell group, sometimes called the chief sensory nucleus, is associated with mechanical and temperature sensations. It is a poorly defined cell column which extends through all segments of the spinal cord and its neurons contribute to ventral and lateral spinal thalamic tracts, as well as to spinal cerebellar tracts. The axons originating in nucleus proprius project to the thalamus via the spinothalamic tract and to the cerebellum via the ventral spinocerebellar tract (VSCT).

Dorsal nucleus of Clarke is a cell column located in the mid-portion of the base form of the dorsal horn. The axons from these cells pass uncrossed to the lateral funiculus and form the dorsal (posterior) spinocerebellar tract (DSCT), which subserve unconscious proprioception from muscle spindles and Golgi tendon organs to the cerebellum, and some of them innervate spinal interneurons. The dorsal nucleus of Clarke is found only in segments C8 to L3 of the spinal cord and is most prominent in lower thoracic and upper lumbar segments. The homologous dorsal nucleus of Clarke in the medulla is the accessory cuneate nucleus, which is the origin of the cuneocerebellar tract (CCT).

Intermediolateral nucleus is located in the intermediate zone between the dorsal and the ventral horns in the spinal cord levels. Extending from C8 to L3, it receives viscerosensory information and contains preganglionic sympathetic neurons, which form the lateral horn. A large proportion of its cells are root cells which send axons into the ventral spinal roots via the white rami to reach the sympathetic tract as preganglionic fibers. Similarly, cell columns in the intermediolateral nucleus located at the S2 to S4 levels contains preganglionic parasympathetic neurons (Figure 3.7).

Lower motor neuron nuclei are located in the ventral horn of the spinal cord. They contain predominantly motor nuclei consisting of , and motor neurons and are found at all levels of the spinal cord--they are root cells. The a motor neurons are the final common pathway of the motor system, and they innervate the visceral and skeletal muscles.

3.7 Rexed Laminae

The distribution of cells and fibers within the gray matter of the spinal cord exhibits a pattern of lamination. The cellular pattern of each lamina is composed of various sizes or shapes of neurons (cytoarchitecture) which led Rexed to propose a new classification based on 10 layers (laminae). This classification is useful since it is related more accurately to function than the previous classification scheme which was based on major nuclear groups (Figure 3.7).

Laminae I to IV, in general, are concerned with exteroceptive sensation and comprise the dorsal horn, whereas laminae V and VI are concerned primarily with proprioceptive sensations. Lamina VII is equivalent to the intermediate zone and acts as a relay between muscle spindle to midbrain and cerebellum, and laminae VIII-IX comprise the ventral horn and contain mainly motor neurons. The axons of these neurons innervate mainly skeletal muscle. Lamina X surrounds the central canal and contains neuroglia.

Rexed lamina I Consists of a thin layer of cells that cap the tip of the dorsal horn with small dendrites and a complex array of nonmyelinated axons. Cells in lamina I respond mainly to noxious and thermal stimuli. Lamina I cell axons join the contralateral spinothalamic tract; this layer corresponds to nucleus posteromarginalis.

Rexed lamina II Composed of tightly packed interneurons. This layer corresponds to the substantia gelatinosa and responds to noxious stimuli while others respond to non-noxious stimuli. The majority of neurons in Rexed lamina II axons receive information from sensory dorsal root ganglion cells as well as descending dorsolateral fasciculus (DLF) fibers. They send axons to Rexed laminae III and IV (fasciculus proprius). High concentrations of substance P and opiate receptors have been identified in Rexed lamina II. The lamina is believed to be important for the modulation of sensory input, with the effect of determining which pattern of incoming information will produce sensations that will be interpreted by the brain as being painful.

Rexed lamina III Composed of variable cell size, axons of these neurons bifurcate several times and form a dense plexus. Cells in this layer receive axodendritic synapses from A fibers entering dorsal root fibers. It contains dendrites of cells from laminae IV, V and VI. Most of the neurons in lamina III function as propriospinal/interneuron cells.

Rexed lamina IV The thickest of the first four laminae. Cells in this layer receive A axons which carry predominantly non-noxious information. In addition, dendrites of neurons in lamina IV radiate to lamina II, and respond to stimuli such as light touch. The ill-defined nucleus proprius is located in the head of this layer. Some of the cells project to the thalamus via the contralateral and ipsilateral spinothalamic tract.

Rexed lamina V Composed neurons with their dendrites in lamina II. The neurons in this lamina receive monosynaptic information from A, Ad and C axons which also carry nociceptive information from visceral organs. This lamina covers a broad zone extending across the neck of the dorsal horn and is divided into medial and lateral parts. Many of the Rexed lamina V cells project to the brain stem and the thalamus via the contralateral and ipsilateral spinothalamic tract. Moreover, descending corticospinal and rubrospinal fibers synapse upon its cells.

Rexed lamina VI Is a broad layer which is best developed in the cervical and lumbar enlargements. Lamina VI divides also into medial and lateral parts. Group Ia afferent axons from muscle spindles terminate in the medial part at the C8 to L3 segmental levels and are the source of the ipsilateral spinocerebellar pathways. Many of the small neurons are interneurons participating in spinal reflexes, while descending brainstem pathways project to the lateral zone of Rexed layer VI.

Rexed lamina VII This lamina occupies a large heterogeneous region. This region is also known as the zona intermedia (or intermediolateral nucleus). Its shape and boundaries vary along the length of the cord. Lamina VII neurons receive information from Rexed lamina II to VI as well as visceral afferent fibers, and they serve as an intermediary relay in transmission of visceral motor neurons impulses. The dorsal nucleus of Clarke forms a prominent round oval cell column from C8 to L3. The large cells give rise to uncrossed nerve fibers of the dorsal spinocerebellar tract (DSCT). Cells in laminae V to VII, which do not form a discrete nucleus, give rise to uncrossed fibers that form the ventral spinocerebellar tract (VSCT). Cells in the lateral horn of the cord in segments T1 and L3 give rise to preganglionic sympathetic fibers to innervate postganglionic cells located in the sympathetic ganglia outside the cord. Lateral horn neurons at segments S2 to S4 give rise to preganglionic neurons of the sacral parasympathetic fibers to innervate postganglionic cells located in peripheral ganglia.

Rexed lamina VIII Includes an area at the base of the ventral horn, but its shape differs at various cord levels. In the cord enlargements, the lamina occupies only the medial part of the ventral horn, where descending vestibulospinal and reticulospinal fibers terminate. The neurons of lamina VIII modulate motor activity, most probably via g motor neurons which innervate the intrafusal muscle fibers.

Rexed lamina IX Composed of several distinct groups of large a motor neurons and small and motor neurons embedded within this layer. Its size and shape differ at various cord levels. In the cord enlargements the number of motor neurons increase and they form numerous groups. The motor neurons are large and multipolar cells and give rise to ventral root fibers to supply extrafusal skeletal muscle fibers, while the small motor neurons give rise to the intrafusal muscle fibers. The motor neurons are somatotopically organized.

Rexed lamina X Neurons in Rexed lamina X surround the central canal and occupy the commissural lateral area of the gray commissure, which also contains decussating axons.

In summary, laminae I-IV are concerned with exteroceptive sensations, whereas laminae V and VI are concerned primarily with proprioceptive sensation and act as a relay between the periphery to the midbrain and the cerebellum. Laminae VIII and IX form the final motor pathway to initiate and modulate motor activity via , and motor neurons, which innervate striated muscle. All visceral motor neurons are located in lamina VII and innervate neurons in autonomic ganglia.

3.8 White Matter

Surrounding the gray matter is white matter containing myelinated and unmyelinated nerve fibers. These fibers conduct information up (ascending) or down (descending) the cord. The white matter is divided into the dorsal (or posterior) column (or funiculus), lateral column and ventral (or anterior) column (Figure 3.8). The anterior white commissure resides in the center of the spinal cord, and it contains crossing nerve fibers that belong to the spinothalamic tracts, spinocerebellar tracts, and anterior corticospinal tracts. Three general nerve fiber types can be distinguished in the spinal cord white matter: 1) long ascending nerve fibers originally from the column cells, which make synaptic connections to neurons in various brainstem nuclei, cerebellum and dorsal thalamus, 2) long descending nerve fibers originating from the cerebral cortex and various brainstem nuclei to synapse within the different Rexed layers in the spinal cord gray matter, and 3) shorter nerve fibers interconnecting various spinal cord levels such as the fibers responsible for the coordination of flexor reflexes. Ascending tracts are found in all columns whereas descending tracts are found only in the lateral and the anterior columns.

Figure 3.8 The spinal cord white matter and its three columns, and the topographical location of the main ascending spinal cord tracts.

Four different terms are often used to describe bundles of axons such as those found in the white matter: funiculus, fasciculus, tract, and pathway. Funiculus is a morphological term to describe a large group of nerve fibers which are located in a given area (e.g., posterior funiculus). Within a funiculus, groups of fibers from diverse origins, which share common features, are sometimes arranged in smaller bundles of axons called fasciculus, (e.g., fasciculus proprius [Figure 3.8]). Fasciculus is primarily a morphological term whereas tracts and pathways are also terms applied to nerve fiber bundles which have a functional connotation. A tract is a group of nerve fibers which usually has the same origin, destination, and course and also has similar functions. The tract name is derived from their origin and their termination (i.e., corticospinal tract - a tract that originates in the cortex and terminates in the spinal cord; lateral spinothalamic tract - a tract originated in the lateral spinal cord and ends in the thalamus). A pathway usually refers to the entire neuronal circuit responsible for a specific function, and it includes all the nuclei and tracts which are associated with that function. For example, the spinothalamic pathway includes the cell bodies of origin (in the dorsal root ganglia), their axons as they project through the dorsal roots, synapses in the spinal cord, and projections of second and third order neurons across the white commissure, which ascend to the thalamus in the spinothalamic tracts.

3.9 Spinal Cord Tracts

The spinal cord white matter contains ascending and descending tracts.

Ascending tracts (Figure 3.8). The nerve fibers comprise the ascending tract emerge from the first order (1) neuron located in the dorsal root ganglion (DRG). The ascending tracts transmit sensory information from the sensory receptors to higher levels of the CNS. The ascending gracile and cuneate fasciculi occupying the dorsal column, and sometimes are named the dorsal funiculus. These fibers carry information related to tactile, two point discrimination of simultaneously applied pressure, vibration, position, and movement sense and conscious proprioception. In the lateral column (funiculus), the neospinothalamic tract (or lateral spinothalamic tract) is located more anteriorly and laterally, and carries pain, temperature and crude touch information from somatic and visceral structures. Nearby laterally, the dorsal and ventral spinocerebellar tracts carry unconscious proprioception information from muscles and joints of the lower extremity to the cerebellum. In the ventral column (funiculus) there are four prominent tracts: 1) the paleospinothalamic tract (or anterior spinothalamic tract) is located which carry pain, temperature, and information associated with touch to the brain stem nuclei and to the diencephalon, 2) the spinoolivary tract carries information from Golgi tendon organs to the cerebellum, 3) the spinoreticular tract, and 4) the spino-tectal tract. Intersegmental nerve fibers traveling for several segments (2 to 4) and are located as a thin layer around the gray matter is known as fasciculus proprius, spinospinal or archispinothalamic tract. It carries pain information to the brain stem and diencephalon.

Descending tracts (Figure 3.9). The descending tracts originate from different cortical areas and from brain stem nuclei. The descending pathway carry information associated with maintenance of motor activities such as posture, balance, muscle tone, and visceral and somatic reflex activity. These include the lateral corticospinal tract and the rubrospinal tracts located in the lateral column (funiculus). These tracts carry information associated with voluntary movement. Other tracts such as the reticulospinal vestibulospinal and the anterior corticospinal tract mediate balance and postural movements (Figure 3.9). Lissauer's tract, which is wedged between the dorsal horn and the surface of the spinal cord carry the descending fibers of the dorsolateral funiculus (DFL), which regulate incoming pain sensation at the spinal level, and intersegmental fibers. Additional details about ascending and descending tracts are described in the next few chapters.

Figure 3.9 The main descending spinal cord tracts.

3.10 Dorsal Root

Figure 3.10 Spinal cord section with its ventral and dorsal root fibers and ganglion.

Information from the skin, skeletal muscle and joints is relayed to the spinal cord by sensory cells located in the dorsal root ganglia. The dorsal root fibers are the axons originated from the primary sensory dorsal root ganglion cells. Each ascending dorsal root axon, before reaching the spinal cord, bifurcates into ascending and descending branches entering several segments below and above their own segment. The ascending dorsal root fibers and the descending ventral root fibers from and to discrete body areas form a spinal nerve (Figure 3.10). There are 31 paired spinal nerves. The dorsal root fibers segregate into lateral and medial divisions. The lateral division contains most of the unmyelinated and small myelinated axons carrying pain and temperature information to be terminated in the Rexed laminae I, II, and IV of the gray matter. The medial division of dorsal root fibers consists mainly of myelinated axons conducting sensory fibers from skin, muscles and joints; it enters the dorsal/posterior column/funiculus and ascend in the dorsal column to be terminated in the ipsilateral nucleus gracilis or nucleus cuneatus at the medulla oblongata region, i.e., the axons of the first-order (1) sensory neurons synapse in the medulla oblongata on the second order (2) neurons (in nucleus gracilis or nucleus cuneatus). In entering the spinal cord, all fibers send collaterals to different Rexed lamina.

Axons entering the cord in the sacral region are found in the dorsal column near the midline and comprise the fasciculus gracilis, whereas axons that enter at higher levels are added in lateral positions and comprise the fasciculus cuneatus (Figure 3.11). This orderly representation is termed somatotopic representation.

Figure 3.11 Somatotopical representation of the spinal thalamic tract and the dorsal column.

3.11 Ventral Root

Ventral root fibers are the axons of motor and visceral efferent fibers and emerge from poorly defined ventral lateral sulcus as ventral rootlets. The ventral rootlets from discrete spinal cord section unite and form the ventral root, which contain motor nerve axons from motor and visceral motor neurons. The motor nerve axons innervate the extrafusal muscle fibers while the small motor neuron axons innervate the intrafusal muscle fibers located within the muscle spindles. The visceral neurons send preganglionic fibers to innervate the visceral organs. All these fibers join the dorsal root fibers distal to the dorsal root ganglion to form the spinal nerve (Figure 3.10).

3.12 Spinal Nerve Roots

The spinal nerve roots are formed by the union of dorsal and ventral roots within the intervertebral foramen, resulting in a mixed nerve joined together and forming the spinal nerve (Figure 3.10). Spinal nerve rami include the dorsal primary nerves (ramus), which innervates the skin and muscles of the back, and the ventral primary nerves (ramus), which innervates the ventral lateral muscles and skin of the trunk, extremities and visceral organs. The ventral and dorsal roots also provide the anchorage and fixation of the spinal cord to the vertebral cauda.

3.13 Blood Supply of the Spinal Cord

The arterial blood supply to the spinal cord in the upper cervical regions is derived from two branches of the vertebral arteries, the anterior spinal artery and the posterior spinal arteries (Figure 3.12). At the level of medulla, the paired anterior spinal arteries join to form a single artery that lies in the anterior median fissure of the spinal cord. The posterior spinal arteries are paired and form an anastomotic chain over the posterior aspect of the spinal cord. A plexus of small arteries, the arterial vasocorona, on the surface of the cord constitutes an anastomotic connection between the anterior and posterior spinal arteries. This arrangement provides uninterrupted blood supplies along the entire length of the spinal cord.

Figure 3.12 The spinal cord arterial circulation.

At spinal cord regions below upper cervical levels, the anterior and posterior spinal arteries narrow and form an anastomotic network with radicular arteries. The radicular arteries are branches of the cervical, trunk, intercostal & iliac arteries. The radicular arteries supply most of the lower levels of the spinal cord. There are approximately 6 to 8 pairs of radicular arteries supplying the anterior and posterior spinal cord (Figure 3.12).

Test Your Knowledge

The spinal cord...

A. Occupies the lumbar cistern

B. Has twelve (12) cervical segments

C. Contains the cell bodies of postganglionic sympathetic efferent neurons

D. Ends at the conus medullaris

E. Has no arachnoid membrane

The spinal cord...

A. Occupies the lumbar cistern This answer is INCORRECT.

The spinal cord does not occupy the lumbar cistern.

B. Has twelve (12) cervical segments

C. Contains the cell bodies of postganglionic sympathetic efferent neurons

D. Ends at the conus medullaris

E. Has no arachnoid membrane

The spinal cord...

A. Occupies the lumbar cistern

B. Has twelve (12) cervical segments This answer is INCORRECT.

The spinal cord has seven (7) cervical segments.

C. Contains the cell bodies of postganglionic sympathetic efferent neurons

D. Ends at the conus medullaris

E. Has no arachnoid membrane

The spinal cord...

A. Occupies the lumbar cistern

B. Has twelve (12) cervical segments

C. Contains the cell bodies of postganglionic sympathetic efferent neurons This answer is INCORRECT.

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Anatomy of the Spinal Cord (Section 2, Chapter 3 ...

Spinal Cord Stem Cells Comments Off on Anatomy of the Spinal Cord (Section 2, Chapter 3 … | November 2nd, 2015

An illustration of GRNOPC1, a drug based on human embryonic stem cells, which contains oligodendrocyte progenitor cells.

Geron/UC Irvine

The hope: that one day this treatment may help the paralyzed walk again.

On Friday at the Shepherd Center, a spinal cord and brain injury rehabilitation center in Atlanta, a patient with a recent spinal cord injury made medical history: The paraplegic was injected with two million embryonic stem cells.

The goal: To regenerate spinal cord tissue.

The process, reports CBS Station KPIX correspondent Dr. Kim Mulvihill, involves coaxing the cells into becoming specialized nerve cells, and then injecting them directly into the injured area of the spinal cord.

The embryonic stem cells come from a donated human embryo left over from a fertility treatment, an embryo that would have otherwise been discarded.

Embryonic stem cells have been at the center of funding controversies because the research involves destroying the embryos, which some have argued is akin to abortion. But, many researchers consider embryonic stem cells the most versatile types of stem cells, as they can morph into any type of cell.

While there are some restrictions on federal funding for stem cell lines for research, companies such as Geron do not use federal funding and are therefore free from those restrictions.

The study is approved by the FDA but is privately funded.

The drug - known as GRNOPC1 - contains cells called oligodendrocyte progenitor cells. Those progenitor cells turn into oligodendrocytes, a type of cell that produces myelin, a coating that allows impulses to move along nerves. When those cells are lost because of injury, paralysis can follow.

If GRNOPC1 works, the progenitor cells will produce new oligodendrocytes in the injured area of the patient's spine, potentially allowing for new movement.

The therapy will be injected into the patients' spines one to two weeks after they suffer an injury between their third and 10th thoracic vertebrae, or roughly the middle to upper back. Later trials would include patients with less severe spinal injuries and damage to other parts of the spine.

In lab animals, the results were dramatic - paralyzed rodents moved again.

Dr. Thomas Okarma, President and CEO of Geron, told CBS Station KPIX, "This therapy goes far beyond the reach of pills or scalpels and will achieve a new level of healing with a single injection of healthy replacement cells."

So far, Geron of Menlo Park, Calif., has spent $175 million in developing this treatment.

However, Dr. Arnold Kriegstein, who heads Regeneration Medicine & Stem Cell Research at University of California-San Francisco, told KPIX, "People are just so different from rodents."

Though optimistic, he urged caution. "I think that people looking at the outcome of this trial should really lower their expectations if they're really thinking people will get out of their wheelchairs. It's unlikely to happen."

The drug still faces many years of testing for effectiveness and tolerance if all goes well in the early stage study.

This initial trial is not aimed at a cure for patients, but to establish if the treatment is safe.

Patients must be treated within 14 days of a spinal cord injury and they must undergo short term immune suppression therapy to make sure their bodies don't reject the cells.

If the treatment is deemed safe, the next trial will aim at testing effectiveness and will use a higher quantity of stem cells.

Shepherd Center is one of seven potential sites in the United States for the trial.

The company has said it plans to enroll eight to 10 patients in the study at sites nationwide. The trial will take about two years, with each patient being studied for one year.

Geron is among several companies focusing on embryonic stem cell therapy. Advanced Cell Technology Inc. hopes to develop the embryonic stem cell therapy called retinal pigment epithelium, or RPE. That therapy is designed to treat Stargart disease, an inherited condition that affects children and can lead to blindness in adulthood.

Meanwhile, other companies such as StemCells Inc. are focusing on adult stem cells, which can be gathered from a person's skin.

For more info: clinicaltrials.goc - Safety Study of GRNOPC1 in Spinal Cord Injury

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Embryonic Stem Cell Test on Spinal Cord Injury - CBS News

Spinal Cord Stem Cells Comments Off on Embryonic Stem Cell Test on Spinal Cord Injury – CBS News | October 4th, 2015