Glial and axonal regeneration following spinal cord injury

Spinal cord injury (SCI) has been regarded clinically as an irreversible damage caused by tissue contusion due to a blunt external force. Past research had focused on the analysis of the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as tissue damage and neural cell death associated with secondary injury. Recent studies, however, have proven that neural stem (progenitor) cells are also present in the brain and spinal cord of adult mammals including humans. Analyses using spinal cord injury models have also demonstrated active dynamics of cells expressing several stem cell markers, and methods aiming at functional reconstruction by promoting the potential self-regeneration capacity of the spinal cord are being explored. Furthermore, reconstruction of the neural circuit requires not only replenishment or regeneration of neural cells but also regeneration of axons. Analysis of the tissue microenvironment after spinal cord injury and research aiming to remove axonal regeneration inhibitors have also made progress. SCI is one of the simplest central nervous injuries, but its pathogenesis is associated with diverse factors, and further studies are required to elucidate these complex interactions in order to achieve spinal cord regeneration and functional reconstruction.     

Glial and axonal regeneration following spinal cord injury

Spinal cord injury (SCI) has been regarded clinically as an irreversible damage caused by tissue contusion due to a blunt external force. Past research had focused on the analysis of the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as tissue damage and neural cell death associated with secondary injury. Recent studies, however, have proven that neural stem (progenitor) cells are also present in the brain and spinal cord of adult mammals including humans. Analyses using spinal cord injury models have also demonstrated active dynamics of cells expressing several stem cell markers, and methods aiming at functional reconstruction by promoting the potential self-regeneration capacity of the spinal cord are being explored. Furthermore, reconstruction of the neural circuit requires not only replenishment or regeneration of neural cells but also regeneration of axons. Analysis of the tissue microenvironment after spinal cord injury and research aiming to remove axonal regeneration inhibitors have also made progress. SCI is one of the simplest central nervous injuries, but its pathogenesis is associated with diverse factors, and further studies are required to elucidate these complex interactions in order to achieve spinal cord regeneration and functional reconstruction.Key words: glia, regeneration, spinal cord, injury, axon     

铁死亡参与脊髓损伤调控的研究进展

铁死亡是一种铁依赖性的,以细胞内脂质活性氧堆积为特征的细胞程序性死亡方式。广泛存在于肿瘤、癌症、急性肾损伤等多种疾病当中。脊髓损伤(spinal cord injury, SCI) 是一种严重的创伤性神经系统疾病,具有高发病率、高死亡率、高致残率的特点。目前,脊髓损伤的具体发生机制及高效治疗方法仍在探索当中,这也是亟待解决的世界性难题。研究表明,脊髓损伤后调控神经细胞的程序性死亡是治疗SCI的重点。然而,对于铁死亡参与脊髓损伤的分子生物学机制尚缺乏系统和深入的认识。收集和整理了近几年国内外有关脊髓损伤后铁死亡方面的相关文献,针对铁死亡参与脊髓损伤的调控机制和研究进展进行了综述,以期为治疗脊髓损伤带来新的思路。     

Prise en charge des troubles de la reproduction de la femme blessée médullaire

The overall outcomes of pregnancies and deliveries in spinal cord injured women are generally favorable. However, several antepartum complications may occur, the most frequent being urinary tract infection. There is also a risk of pressure sores and thrombophlebitis. Autonomic hyperreflexia is a serious problem and a potential danger to spinal cord injured women with neurological levels above T6, particularly during the third trimester and during labor. Autonomic hyperreflexia is generally prevented by continuous epidural anesthesia. Concerning the mode of delivery, most patients are able to deliver vaginally, but forceps are sometimes necessary. Cesarean section must only be performed for obstetric reasons and in cases of intractable autonomic hyperreflexia.     

Infant survival in prematurity

Reduction of neonatal mortality and the rate of stillbirth may be expected from improved management of spontaneous labor and delivery.Neither roentgenographic measurement nor the inception of fetal movement or heartbeat nor any other single test is an index of fetal maturity; all must be considered together. Prenatal care, particularly supplemented diet, will help to avoid premature delivery, or at least to prolong pregnancy; since the fetus undergoes accelerated growth during the last weeks of pregnancy, even slight extension of gestation increases the chances for survival. Analgesia in the first stage of premature labor is contraindicated. Only low spinal anesthesia and other types of conduction anesthesia should be employed for later stages. The fetal membranes should be preserved as long as possible, but premature rupture does not call for immediate termination of pregnancy. Deep episiotomy and prophylactic outlet forceps are routinely employed to hasten the second stage of premature delivery and to protect the immature fetus. Breech presentation is managed by unassisted expulsion or by forceps extraction of the head. The umbilical cord is not immediately severed on delivery; administration of oxytocic drugs after the second stage of labor, combined with gentle stripping of the cord, results in rapid transfer of increased amount of placental blood. The airways of the infant should be immediately cleared. Artificial respiration may be necessary and it must be gentle.All premature infants should receive supplementary oxygen to render breathing regular and more efficient. They should be insulated immediately in controlled temperature and humidity, and they should be handled little.     

Dietary Supplementation with Organoselenium Accelerates Recovery of Bladder Expression,but Does Not Improve Locomotor Function,following Spinal Cord Injury

Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. However, this was not accompanied by improvement in locomotor function or tissue sparing.     

丁酸盐与β-羟基丁酸盐在脊髓损伤中的抗炎作用

脊髓损伤是一种严重的疾病,目前尚无有效的治疗方法。炎症反应在脊髓损伤后数h内开始,在几d内达到峰值,并可能持续数y。减轻脊髓损伤后的炎症反应是重要的治疗策略之一。丁酸盐与β-羟基丁酸盐是2种密切相关的物质,2者结构相似,仅有1个羟基不同,因在多种疾病中显现出良好的抗炎特性而引起广泛关注。近期有基础研究发现,丁酸盐与β-羟基丁酸盐可以抑制NF-κB/ NLRP3炎性小体信号通路活性,降低促炎因子表达;或通过增加抗氧化分子的水平,减轻脊髓损伤后炎症反应。因此,丁酸盐与β-羟基丁酸盐可能是脊髓损伤后有前景的治疗方法。本文拟对丁酸盐与β-羟基丁酸盐的结构与产生、在脊髓损伤中发挥抗炎作用的机制、治疗前景进行综述,以期为该领域科研人员提供理论参考。     

Neuropeptides in spinal cord injury: Comparative experimental models

The possible role of endogenous opioids in the pathophysiology of spinal cord injury was evaluated utilizing a variety of experimental models and species. In the cat, we have shown that β-endorphin-like immunoreactivity was increased in plasma following traumatic spinal injury; such injury was associated with a decrease in spinal cord blood flow (SCBF) which was reversed by the opiate receptor antagonist naloxone. Naloxone treatment also significantly improved functional neurological recovery after severe injury. Thyrotropin-releasing hormone (TRH), possibly through its “anti-endorphin” actions, was even more effective than naloxone in improving functional recovery in the cat. In a rat model, utilizing a similar trauma method, TRH proved superior to naloxone in improving SCBF after injury. In addition, naloxone at high doses attenuated the hindlimb paralysis produced by temporary aortic occlusion in the rabbit. The high doses of naloxone required to improve neurological function after spinal injury suggest that naloxone's actions, if opiate receptor mediated, may be mediated by non-μ receptors. Dynorphin, an endogenous opioid with a high affinity for the κ receptor, produced hindlimb paralysis following intrathecal administration in rats. Taken together, these findings suggest that endogenous opioids, possibly acting at κ receptors in the spinal cord, may serve as pathophysiological factors in spinal cord injury.     

脊髓损伤的病理变化及治疗进展

脊髓损伤是中枢神经系统严重的创伤,多为脊柱损伤的最严重并发症之一,常造成损伤平面以下的肢体运动、感觉及植物神经功能紊乱,不仅给患者本人带来常人难以想象的心理痛苦及生活障碍,给家庭及社会同样带来高额的负担。近年来,脊髓损伤呈现出高发病率、高耗费、高致残率及低龄化的"三高一低"的发病趋势,逐渐成为学术界急需攻克的重大医疗问题。随着脊髓损伤病理生理机制的深入研究,针对发病机制不同阶段进行阻断的新药研究成为热点,加上干细胞技术及生物工程的发展,均为脊髓损伤后的治疗提供了新的方向。     

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation,Postural Instability and Pasta Handling

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.     

Phospholipids of normal and experimentally injured spinal cord of the miniature pig

Experimental spinal cord trauma was produced in 3-month-old SS-1 minature pigs by dropping a 25 g weight from a height of 20 cm upon the exposed spinal cord. The histological lesion consisted of edema and hemorrhage. Phospholipid concentration and composition, cholesterol concentration and phospholipid fatty acid composition were determined in whole spinal cord 3 hours after injury, and in spinal cord myelin 5 hours after injury. Three hours after injury phospholipid and cholesterol concentration were decreased by about 14% in the whole spinal cord. Trauma had no effect on the phospholipid composition of whole spinal cord and myelin. Fatty acid composition of myelin also did not change after injury, and changed very slightly in the whole spinal cord. It is concluded that edema following spinal cord trauma is much more extensive than previously assumed. Furthermore, peroxidation of membrane lipid fatty acids does not appear to be a significant factor in spinal cord pathology 3 hours after injury.     

Treatment of Upper Cervical Spine Instability with Posterior Fusion Plus Atlantoaxial Pedicle Screw

Clinical results of posterior fusion plus pedicle screw fixation in the treatment of upper cervical spine instability were taken under consideration. 24 patients with atlantoaxial instability were treated with C1-2 pedicle screws and rods fixation under general anesthesia. There were 18 males and 6 females with mean age of 49.8 years (age range 17–69 years). The postoperative radiographs verified good position of all screws, with satisfactory atlantoaxial reduction. Follow-up for 3–45 months (average 23 months) showed no spinal cord and vertebral artery injury or interfixation failure. Atlantoaxial alignment and stability were restored without complication due to instrumentation. In conclusion, posterior atlantoaxial pedicle screw and rod fixation provide immediate three-dimensional rigid fixation of atlantoaxial joint and are more effective techniques compared with previously reported techniques.     

Delaying childbearing: effect of age on fecundity and outcome of pregnancy.

OBJECTIVES--To study the age of the start of the fall (critical age) in fecundity; the probability of a pregnancy leading to a healthy baby taking into account the age of the woman; and, combining these results, to determine the age dependent probability of getting a healthy baby. DESIGN--Cohort study of all women who had entered a donor insemination programme. SETTING--Two fertility clinics serving a large part of The Netherlands. SUBJECTS--Of 1637 women attending for artificial insemination 751 fulfilled the selection criteria, being married to an azoospermic husband and nulliparous and never having received donor insemination before. MAIN OUTCOME MEASURES--The number of cycles before pregnancy (a positive pregnancy test result) or stopping treatment; and result of the pregnancy (successful outcome). RESULTS--Of the 751 women, 555 became pregnant and 461 had healthy babies. The fall in fecundity was estimated to start at around 31 years (critical age); after 12 cycles the probability of pregnancy in a woman aged greater than 31 was 0.54 compared with 0.74 in a woman aged 20.31. After 24 cycles this difference had decreased (probability of conception 0.75 in women greater than 31 and 0.85 in women 20.31). The probability of having a healthy baby also decreased--by 3.5% a year after the age of 30. Combining both these age effects, the chance of a woman aged 35 having a healthy baby was about half that of a woman aged 25. CONCLUSION--After the age of 31 the probability of conception falls rapidly, but this can be partly compensated for by continuing insemination for more cycles. In addition, the probability of an adverse pregnancy outcome starts to increase at about the same age.     

Expression of neural cell adhesion molecule in spinal cords following a complete transection

Neural cell adhesion molecule (NCAM) regulates tissue organization during development and in the adult. NCAM upregulation occurs after an injury to brains and sciatic nerves. However, little is known about NCAM expression after spinal cord injury (SCI). By using a complete spinal cord transection with a 5 mm tissue removal, an increase in the NCAM level is detected in spinal cord stumps proximal and distal to the transection site at 1 d and 3 d post injury, while its expression at 8 d is declined to a lower level than that observed in sham-operated spinal cords. The strong NCAM expression is present in motor neurons at 3 d post transection whereas the intensive NCAM immunostaining is localized in dorsal sensory and corticospinal fiber tracts at 8 d following injury. Collectively, NCAM level is elevated and strongly expressed in dorsal fiber tracts after SCI, implying that the endogenous process for spinal cord regeneration may take place after SCI.     

Perinatal outcome analysis of twin pregnancies at the Department of Obstetrics and Gynecology Central Clinical Hospital of Ministry of Interior and Administration in Warsaw in the years 2005-2006

A group of 59 twin pregnant women who gave birth at the Department of Obstetrics and Gynecology Central Clinical Hospital of Ministry of Interior and Administration in Warsaw in the years 2005-2006. The patients have been divided into four groups: spontaneous twin pregnant women (n=16), twin pregnant women after in- vitro fertilization (IVF) (n=11), twin pregnant women after in-vitro fertilization with intracytoplasmic sperm injection (ICSI) (n=29) and twin pregnant women after ICSI and transfer of frozen embryos (n=3). In one case intrauterine death of one of twins in the 34th week of gestation has been noticed. The cause of the death was umbilical cord wrapped around his neck. The gestation was ended with cesarean section and Apgar score of the second twin was 8 in the fifth minute. In one case there was an urgent indication for a cesarean delivery of children with a very low birth weight (because of intrauterine infection, preterm labor in progress) and in three cases at least one of twins with a low birth weight. Among the group 19 women (32%) have given birth prematurely. The Apgar score in the first, third and fifth minute has been statistically significant and inversely proportional dependent only on the gestational age. There were no differences in birth weight among study groups regardless the way of conception. Only two spontaneous twin pregnant patients have had a vaginal labor. By the remaining 57 patients there has been an elective cesarean section in thirty five cases and there has been an urgent indication for cesarean section in twenty two cases.     

Spinal cord evoked potentials and edema in the pathophysiology of rat spinal cord injury

Summary The possibility that nitric oxide is somehow involved in the early bioelectrical disturbances following spinal cord injury in relation to the later pathophysiology of the spinal cord was examined in a rat model of spinal cord trauma. A focal trauma to the rat spinal cord was produced by an incision of the right dorsal horn of the T 10–11 segments under urethane anaesthesia. The spinal cord evoked potentials (SCEP) were recorded using epidural electrodes placed over the T9 and T12 segments of the cord following supramaximal stimulation of the right tibial and sural nerves in the hind leg. Trauma to the spinal cord significantly attenuated the SCEP amplitude (about 60%) immediately after injury which persisted up to 1h. However, a significant increase in SCEP latency was seen at the end of 5h after trauma. These spinal cord segments exhibited profound upregulation of neuronal nitric oxide synthase (NOS) immunoreactivity, and the development of edema and cell injury. Pretreatment with a serotonin synthesis inhibitor drug p-chlorophenylalanine (p-CPA) or an anxiolytic drug diazepam significantly attenuated the decrease in SCEP amplitude, upregulation of NOS, edema and cell injury. On the other hand, no significant reduction in SCEP amplitude, NOS immunolabelling, edema or cell changes were seen after injury in rats pretreated with L-NAME. These observations suggest that nitric oxide is somehow involved in the early disturbances of SCEP and contribute to the later pathophysiology of spinal cord injury.     

The mechanical properties of neonatal rat spinal cord in vitro,and comparisons with adult

A number of studies have investigated the mechanical properties of adult spinal cord under tension, however it is not known whether age has an effect on these properties. This is of interest to those aiming to understand the clinical differences between adults and children with spinal cord injury (e.g. severity and recovery), and those developing experimental or computational models for paediatric spinal cord injury. Entire spinal cords were freshly harvested from neonatal rats (14 days) and tested in vitro under uniaxial tension at a range of strain rates (0.2, 0.02, 0.002/s) to a range of strains (2%, 3.5%, 5%), with relaxation responses being recorded for 15 min. These mechanical properties were compared to previously reported data from similar experiments on adult rat spinal cords, and the peak stress and the stress after 15 min of relaxation were found to be significantly higher for spinal cords from adults than neonates (p<0.001). A non-linear viscoelastic model was developed and was observed to adequately predict the mechanical behaviour of this tissue. The model developed in this study may be of use in computational models of paediatric spinal cord. The significant differences between adult and neonatal spinal cord properties may explain the higher initial severity of spinal cord injury in children and may have implications for the development of experimental animal models for paediatric spinal cord injury, specifically for those aiming to match the injury severity with adult experimental models.     

脊髓缺血再灌注损伤的防治概况

脊髓缺血-再灌注损伤(SCII)是一种严重的神经系统损伤,是缺血脊髓组织恢复血液灌注后,脊髓组织的损伤反而加重,表现为其神经损害体征和形态学改变较前更加明显,其发生机制是多因素的综合结果,治疗措施也具有多样性,脊髓缺血后脊髓微血管结构及功能的破坏和脊髓水肿等是脊髓功能损害的主要诱因,至今为止,脊髓缺血再灌注损伤的防治主要有药物及物理治疗等方法,本文作者通过查阅中外文献对脊髓缺血再灌注损伤的特征、发生机制及防治措施作一综述,希望对研究脊髓缺血再灌注损伤防治的学者能有所帮助。