The glial scar in spinal cord injury and repair

Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCI) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCI. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCI.     

Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries

The formation of misaligned scar tissue by a variety of cell types expressing multiple axon growth inhibitory proteoglycans presents a physical and molecular barrier to axon regeneration after adult spinal cord injuries. Decorin is a small, leucine-rich proteoglycan that has previously been shown to reduce astrogliosis and basal lamina formation in acute cerebral cortex stab injuries. We have therefore tested whether mini pump infusion of hr-decorin into acute stab injuries of the adult rat spinal cord can not only inhibit formation of an astroglial limitans but also deposition of the axon growth inhibitory proteoglycans neurocan, NG2, phosphacan and brevican. Combined immunohistochemical and quantitative Western blot analysis revealed major reductions in levels of core protein expression (>80% for 130-kDa neurocan, 145/80-kDa brevican, 300-kDa phosphacan) and immunoreactivity for all four chondroitin sulfate proteoglycans (CSPGs) within decorin-treated injuries compared with untreated controls. Astrogliosis within lesion margins and the accumulation of OX42+ macrophages/microglia within lesion centres were also significantly reduced. These decorin-induced changes in scar formation combined to promote the striking ability of axons from microtransplanted adult sensory neurons to enter, grow within and exit decorin-infused spinal cord injuries, in sharp contrast to the complete failure of axons to cross untreated, CSPG-rich lesions. Decorin pretreatment of meningial fibroblasts in vitro also resulted in a three-fold increase in neurite outgrowth from co-cultured adult sensory neurons and suppression of NG2 immunoreactivity. The ability of decorin to promote axon growth across acute spinal cord injuries via a coordinated suppression of inflammation, CSPG expression and astroglial scar formation make decorin treatment a promising component of future spinal cord regeneration strategies.     

Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury

Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the cells that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of the spinal cord, especially the inflammatory cytokines that dramatically increase in the acute phase at the injury site, is considered to be an important cause of inhibitory mechanism of neuronal differentiation following SCI. Interleukin-6 (IL-6), which has been demonstrated to induce NSPCs to undergo astrocytic differentiation selectively through the JAK/STAT pathway in vitro, has also been demonstrated to play a critical role as a proinflammatory cytokine and to be associated with secondary tissue damage in SCI. In this study, we assessed the efficacy of rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) in the treatment of acute SCI in mice. Immediately after contusive SCI with a modified NYU impactor, mice were intraperitoneally injected with a single dose of MR16-1 (100 microg/g body weight), the lesions were assessed histologically, and the functional recovery was evaluated. MR16-1 not only suppressed the astrocytic diffentiation-promoting effect of IL-6 signaling in vitro but inhibited the development of astrogliosis after SCI in vivo. MR16-1 also decreased the number of invading inflammatory cells and the severity of connective tissue scar formation. In addition, we observed significant functional recovery in the mice treated with MR16-1 compared with control mice. These findings suggest that neutralization of IL-6 signaling in the acute phase of SCI represents an attractive option for the treatment of SCI.     

Synergistic actions of olomoucine and bone morphogenetic protein-4 in axonal repair after acute spinal cord contusion

To determine whether olomoucine acts synergistically with bone morphogenetic protein-4 in the treatment of spinal cord injury, we established a rat model of acute spinal cord contusion by impacting the spinal cord at the T8 vertebra. We injected a suspension of astrocytes derived from glial-restricted precursor cells exposed to bone morphogenetic protein-4 （GDAsBMP） into the spinal cord around the site of the injury, and/or olomoucine intraperitoneally. Olomoucine effectively inhibited astrocyte proliferation and the formation of scar tissue at the injury site, but did not prevent proliferation of GDAsBMP or inhibit their effects in reducing the spinal cord lesion cavity. Furthermore, while GDAsBMP and olomoucine independently resulted in small improve- ments in locomotor function in injured rats, combined administration of both treatments had a significantly greater effect on the restoration of motor function. These data indicate that the combined use of olomoucine and GDAsBMP creates a better environment for nerve regeneration than the use of either treatment alone, and contributes to spinal cord repair after injury.     

Biomaterials for spinal cord repair

Spinal cord injury (SCI) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCI is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCI. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCI. A plethora of biomaterials is available and has been tested in various models of SCI. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi.     

Metamorphosis and the regenerative capacity of spinal cord axons in Xenopus laevis

Throughout the vertebrate subphylum, the regenerative potential of central nervous system axons is greatest in embryonic stages and declines as development progresses. For example, Xenopus laevis can functionally recover from complete transection of the spinal cord as a tadpole but is unable to do so after metamorphosing into a frog. Neurons of the reticular formation and raphe nucleus are among those that regenerate axons most reliably in tadpole and that lose this ability after metamorphosis. To identify molecular factors associated with the success and failure of spinal cord axon regeneration, we pharmacologically manipulated thyroid hormone (TH) levels using methimazole or triiodothyronine, to either keep tadpoles in a permanently larval state or induce precocious metamorphosis, respectively. Following complete spinal cord transection, serotonergic axons crossed the lesion site and tadpole swimming ability was restored when metamorphosis was inhibited, but these events failed to occur when metamorphosis was prematurely induced. Thus, the metamorphic events controlled by TH led directly to the loss of regenerative potential. Microarray analysis identified changes in hindbrain gene expression that accompanied regeneration-permissive and -inhibitory conditions, including many genes in the permissive condition that have been previously associated with axon outgrowth and neuroprotection. These data demonstrate that changes in gene expression occur within regenerating neurons in response to axotomy under regeneration-permissive conditions in which normal development has been suspended, and they identify candidate genes for future studies of how central nervous system axons can successfully regenerate in some vertebrates.     

Examining the properties and therapeutic potential of glial restricted precursors in spinal cord injury

In the aftermath of spinal cord injury, glial restricted precursors (GRPs) and immature astrocytes offer the potential to modulate the inlfammatory environment of the injured spinal cord and promote host axon re-generation. Nevertheless clinical application of cellular therapy for the repair of spinal cord injury requires strict quality-assured protocols for large-scale production and preservation that necessitates long-term in vitro expansion. Importantly, such processes have the potential to alter the phenotypic and functional properties and thus therapeutic potential of these cells. Furthermore, clinical use of cellular therapies may be limited by the inlfammatory microenvironment of the injured spinal cord, altering the phenotypic and functional properties of grafted cells. This report simulates the process of large-scale GRP production and demonstrates the permissive properties of GRP following long-termin vitro culture. Furthermore, we de-ifned the phenotypic and functional properties of GRP in the presence of inlfammatory factors, and call attention to the importance of the microenvironment of grafted cells, underscoring the importance of modulating the environment of the injured spinal cord.     

Lentiviral‐mediated silencing of glial fibrillary acidic protein and vimentin promotes anatomical plasticity and functional recovery after spinal cord injury

In spinal cord injury (SCI), absence of functional recovery and lack of spontaneous axonal regeneration are attributed, among other factors, to the formation of a glial scar that forms both physical and chemical barriers. The glial scar is composed mainly of reactive astrocytes that overexpress two intermediate filament proteins, glial fibrillary acidic protein (GFAP) and vimentin (VIM). To promote regeneration and sprouting of spared axons after spinal cord trauma and with the objective of translation to clinics, we designed an original in vivo gene transfer strategy to reduce glial scar formation after SCI, based on the RNA interference (RNAi)‐mediated inhibition of GFAP and VIM. We first show that direct injection of lentiviral vectors expressing short hairpin RNA (shRNA) against GFAP and VIM in a mouse model of SCI allows efficient and specific targeting of astrocytes. We then demonstrate that the lentiviral‐mediated and stable expression of shGFAP and shVIM leads to a strong reduction of astrogliosis, improves functional motor recovery, and promotes axonal regrowth and sprouting of spared axons. This study thus examplifies how the nonneuronal environment might be a major target within the lesioned central nervous system to promote axonal regeneration (and sprouting) and validates the use of lentiviral‐mediated RNAi in SCI. © 2014 Wiley Periodicals, Inc.     

Telomerase expression in the glial scar of rats with spinal cord injury

A rat model of spinal cord injury was established using the weight drop method. A cavity formed 14 days following spinal cord injury, and compact scar tissue formed by 56 days. Enzyme-linked immunosorbent assay and polymerase chain reaction enzyme-linked immunosorbent assay results demonstrated that glial fibrillary acidic protein and telomerase expression increased gradually after injury, peaked at 28 days, and then gradually decreased. Spearman rank correlation showed a positive correlation between glial fibrillary acidic protein expression and telomerase expression in the glial scar. These results suggest that telomerase promotes glial scar formation.     

MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish

MicroRNAs (miRNAs) play important roles during development and also in adult organisms by regulating the expression of multiple target genes. Here, we studied the function of miR-133b during zebrafish spinal cord regeneration and show upregulation of miR-133b expression in regenerating neurons of the brainstem after transection of the spinal cord. miR-133b has been shown to promote tissue regeneration in other tissue, but its ability to do so in the nervous system has yet to be tested. Inhibition of miR-133b expression by antisense morpholino (MO) application resulted in impaired locomotor recovery and reduced regeneration of axons from neurons in the nucleus of the medial longitudinal fascicle, superior reticular formation and intermediate reticular formation. miR-133b targets the small GTPase RhoA, which is an inhibitor of axonal growth, as well as other neurite outgrowth-related molecules. Our results indicate that miR-133b is an important determinant in spinal cord regeneration of adult zebrafish through reduction in RhoA protein levels by direct interaction with its mRNA. While RhoA has been studied as a therapeutic target in spinal cord injury, this is the first demonstration of endogenous regulation of RhoA by a microRNA that is required for spinal cord regeneration in zebrafish. The ability of miR-133b to suppress molecules that inhibit axon regrowth may underlie the capacity for adult zebrafish to recover locomotor function after spinal cord injury.     

Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury

A large body of evidence shows that spinal circuits are significantly affected by training,and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection.However,after incomplete lesions,the effect of treadmill training has been debated,which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects.In this study,rats with moderate spinal cord contusion were subjected to either step training on a treadmill or used in the model(control) group.The treadmill training began at day 7 post-injury and lasted 20 ± 10 minutes per day,5 days per week for 10 weeks.The speed of the treadmill was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat.After 3 weeks of step training,the step training group exhibited a significantly greater improvement in the Basso,Beattie and Bresnahan score than the model group.The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury,while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups.These results suggest that treadmill training significantly improves functional recovery and neural plasticity after incomplete spinal cord injury.     

Contribution of bone marrow‐derived endothelial progenitor cells to neovascularization and astrogliosis following spinal cord injury

Spinal cord injury causes initial mechanical damage, followed by ischemia‐induced, secondary degeneration, worsening the tissue damage. Although endothelial progenitor cells (EPCs) have been reported to play an important role for pathophysiological neovascularization in various ischemic tissues, the EPC kinetics following spinal cord injury have never been elucidated. In this study, we therefore assessed the in vivo kinetics of bone marrow‐derived EPCs by EPC colony‐forming assay and bone marrow transplantation from Tie2/lacZ transgenic mice into wild‐type mice with spinal cord injury. The number of circulating mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day 3 postspinal cord injury. Bone marrow transplantation study revealed that bone marrow‐derived EPCs recruited into the injured spinal cord markedly increased at day 7, when neovascularization and astrogliosis drastically occurred in parallel with axon growth in the damaged tissue. To elucidate further the contribution of EPCs to recovery after spinal cord injury, exogenous EPCs were systemically infused immediately after the injury. The administered EPCs were incorporated into the injured spinal cord and accelerated neovascularization and astrogliosis. These findings suggest that bone marrow‐derived EPCs may contribute to the tissue repair by augmenting neovascularization and astrogliosis following spinal cord injury. © 2012 Wiley Periodicals, Inc.     

Transplantation of olfactory ensheathing cells promotes axonal regeneration in a rat model of spinal cord injury

BACKGROUND:Transplantation of olfactory ensheathing cells (OECs) into the injured spinal cord has been shown to promote axonal regeneration and functional recovery.However,the mechanisms underlying the effects of OEC transplantation remain controversial.OBJECTIVE:To observe fibrotic scar formation and axonal regeneration in the damaged spinal cord following OEC transplantation,and to determine whether OEC transplantation promotes neural regeneration by attenuating fibrotic scar formation.DESIGN,TIME AND SETTING:A randomized,controlled animal experiment was performed at the Department of Developmental Morphology,Tokyo Metropolitan Institute for Neuroscience,Fuchu,Japan and at the Department of Human Anatomy,College of Basic Medical Sciences,China Medical University,China between April 2007 and May 2009.MATERIALS:OECs were obtained from olfactory nerves and olfactory bulbs of male,4-week-old,Sprague Dawley rats.Rabbit anti-serotonin polyclonal antibody,rabbit anti-calcitonin gene-related peptide polyclonal antibody,rabbit anti-glial fibrillary acidic protein polyclonal antibody,rabbit anti-type IV collagen polyclonal antibody,and mouse anti-rat endothelial cell antigen-1 monoclonal antibody were used.METHODS:Male,Sprague Dawley rats aged 8 weeks were randomly divided into three groups:sham-surgery (n = 3),surgery (n = 9),and OEC transplantation (n = 11).Spinal cord transection at the T9-10 level was performed and the rats were transplanted with a 2-μL (1 × 105 cells) cell suspension.MAIN OUTCOME MEASURES:Formation of glial and fibrotic scars was examined using immunohistochemistry for glial fibrillary acidic protein and type IV collagen.Serotonin-positive and calcitonin gene-related peptide-positive axons were visualized by immunohistochemistry,respectively.Double immunofluorescence for type IV collagen and rat endothelial cell antigen-1 was also performed to determine co-localization of type IV collagen deposition and blood vessels.RESULTS:At 1 week after spinal cord injury,numerous glial cells were observed around the lesion site.Formation of fibrotic scar was determined by a large amount of type IV collagen deposition in the lesion center,and descending serotonin- or ascending calcitonin gene-related peptideconiaining axons stopped at the fibrotic scar that was formed in the lesion site.At week after transplantation,the formation of fibrotic scar was significantly inhibited.In addition,the fibrotic structure was partly formed and centralized in the blood vessel,and serotonergic and calcitonin gene-related peptide-containing axons were regenerated across the lesion site.CONCLUSION:OEC transplantation into the injured spinal cord attenuated fibrotic scar formation and promoted axon regeneration.     

Corticospinal tract regeneration after spinal cord injury in receptor protein tyrosine phosphatase sigma deficient mice

Receptor protein tyrosine phosphatase sigma (RPTPσ) plays a role in inhibiting axon growth during development. It has also been shown to slow axon regeneration after peripheral nerve injury and inhibit axon regeneration in the optic nerve. Here, we assessed the ability of the corticospinal tract (CST) axons to regenerate after spinal hemisection and contusion injury in RPTPσ deficient (RPTPσ^−/−) mice. We show that damaged CST fibers in RPTPσ^−/− mice regenerate and appear to extend for long distances after a dorsal hemisection or contusion injury of the thoracic spinal cord. In contrast, no long distance axon regeneration of CST fibers is seen after similar lesions in wild‐type mice. In vitro experiments indicate that cerebellar granule neurons from RPTPσ^−/− mice have reduced sensitivity to the inhibitory effects of chondroitin sulfate proteoglycan (CSPG) substrate, but not myelin, which may contribute to the growth of CST axons across the CSPG‐rich glial scar. Our data suggest that RPTPσ may function to prevent axonal growth after injury in the adult mammalian spinal cord and could be a target for promoting long distance regeneration after spinal cord injury. © 2009 Wiley‐Liss, Inc.     

MicroRNA‐145 as one negative regulator of astrogliosis

Astrogliosis occurs at the lesion site within days to weeks after spinal cord injury (SCI) and involves the proliferation and hypertrophy of astrocytes, leading to glia scar formation. Changes in gene expression by deregulated microRNAs (miRNAs) are involved in the process of central nervous system neurodegeneration. Here, we report that mir‐145, a miRNA enriched in rat spinal neurons and astrocytes, was downregulated at 1 week and 1 month after SCI. Our in vitro studies using astrocytes prepared from neonatal spinal cord tissues indicated that potent inflammagen lipopolysaccharide downregulated mir‐145 expression in astrocytes, suggesting that SCI‐triggered inflammatory signaling pathways could play the inhibitory role in astrocytic mir‐145 expression. To induce overexpression of mir‐145 in astrocytes at the spinal cord lesion site, we developed a lentivirus‐mediated pre‐miRNA delivery system using the promoter of glial fibrillary acidic protein (GFAP), an astrocyte‐specific intermediate filament. The results indicated that astrocyte‐specific overexpression of mir‐145 reduced astrocytic cell density at the lesion border of the injured spinal cord. In parallel, overexpression of mir‐145 reduced the size of astrocytes and the number of related cell processes, as well as cell proliferation and migration. Through a luciferase reporter system, we found that GFAP and c‐myc were the two potential targets of mir‐145 in astrocytes. Together, the findings demonstrate the novel role of mir‐145 in the regulation of astrocytic dynamics, and reveal that the downregulation of mir‐145 in astrocytes is a critical factor inducing astrogliosis after SCI. GLIA 2015;63:194–205     

Lesional RhoA+ cell numbers are suppressed by anti-inflammatory, cyclooxygenase-inhibiting treatment following subacute spinal cord injury

Inhibition of the small GTPase RhoA or its downstream target Rho-associated coiled kinase (ROCK) has been shown to promote axon regeneration and to improve functional recovery following spinal cord injury (SCI) in the adult rat. RhoA has also been implicated in delayed secondary injury pathophysiology, such as free radical formation and loss of endothelial integrity leading to edema formation. In the present report, we have analyzed the effect of the central nervous system (CNS) permissive, putatively neuroprotective, anti-inflammatory cyclooxygenase-1/-2 (COX-1/-2) inhibitor indomethacin in CNS effective dosage (2 mg/kg/day) on lesional RhoA expression following subacute spinal cord injury. In control rats receiving vehicle alone, RhoA+ cells accumulate at the lesion site (Th8). At day 3 following SCI, the RhoA+ cellular composition is composed prevailingly of microglia/macrophages and polymononuclear granulocytes, but few reactive astrocytes. In contrast, in the verum group, lesional numbers of RhoA cells were reduced by indomethacin treatment by more than 60% (P < 0.0001). Inflammation-dependent RhoA expression accessible by cyclooxygenase inhibition proposes an immune-related mechanism. Our results identify COX blockers as candidates for a safe, synergistic, adjuvant treatment option in combination with cell-specific approaches to Rho inactivation, effectively minimizing the pool of RhoA+ cells at the lesion site following SCI.     

5000/磁性纳米颗粒-Pluronic携带神经节苷脂-1对急性完全横断性脊髓损伤修复的影响(英文发表)

背景：温度敏感性磁性纳米颗粒即磁性纳米颗粒-Pluronic具有温度响应药物控制释放能力,并能穿透血脑屏障。 目的:实验检测其携带神经节苷脂(GM-1)能力及在活体组织中药物释放能力,以及对脊髓损伤修复再生的影响。 设计、时间及地点：随机对照动物实验,于2006-09/2007-02在首都医科大学北京神经科学研究所和中国科学院过程工程研究所完成。 材料：神经节苷脂由阿根廷Trb Pharma药厂生产。磁性纳米颗粒-Pluronic的制备及其负载神经节苷脂由中国科学院过程工程研究所制备。 方法:将20只SD大鼠制作急性完全横断脊髓损伤模型,随机分为4组:①治疗组:于脊髓断端间注射磁性纳米颗粒-Pluronic-GM-1 100 μL+纤维蛋白胶100 μL。②对照组1:于脊髓断端间注射磁性纳米颗粒-Pluronic 100 μL+纤维蛋白胶100 μL。③对照组2:于脊髓断端间注射纤维蛋白胶100 μL。④空白组:单纯横断不予以任何治疗。 主要观察指标：4周后,应用免疫组织化学方法结合图像分析方法,对脊髓横断处远端、近端进行神经纤维计数及胶质细胞网格框架结构定量分析,以了解神经再生情况。 结果:20只大鼠均进入结果分析。①脊髓横断区神经纤维数量:治疗组近端、远端均高于其他3组(P < 0.05),2个对照组高于空白组(P < 0.05),对照组2高于对照组1(P < 0.05)。②脊髓横断区胶质纤维面积比:治疗组近端、远端均高于其他3组(P < 0.05),2个对照组近端明显高于空白组(P < 0.05),对照组2远端高于空白组(P < 0.05)。 结论:磁性纳米颗粒-Pluronic具有药物携带及释放作用,其携带神经节苷脂对脊髓损伤具有一定程度的修复及促进神经再生的作用。     

他克莫司促进神经干细胞移植大鼠脊髓损伤的再生与修复

背景：研究证实,他克莫司不仅抑制T细胞的增殖、活化,还能抑制小胶质细胞、巨噬细胞等炎症细胞在损伤局部聚集、活化及相关炎症因子的释放,减轻继发性炎症反应对原发损伤周围正常组织的破坏,从而对损伤局部的神经组织起保护作用。 目的：观察他克莫司对神经干细胞移植大鼠脊髓损伤后再生修复的影响。 方法：分离培养孕13d SD大鼠神经干细胞。显微镜下动脉瘤夹夹闭SD大鼠T8脊髓,建立压迫型脊髓损伤动物模型。损伤后7 d随机数字表分为3组：对照组,于损伤中心定向注射生理盐水;细胞移植组,于损伤中心定向注射神经干细胞;他克莫司组,于损伤中心定向注射神经干细胞同时给予免疫抑制剂他克莫司1 mg/(kg•d)腹腔注射连续7 d。1,2,4,8周后,通过BDA顺行示踪、苏木精-伊红与免疫组化染色及电镜检测,观察移植后脊髓组织再生和神经元的变化。 结果与结论：对照组在损伤中心端远侧无神经纤维通过。细胞移植组与他克莫司组在治疗1周后有部分神经纤维通过,8周均有部分BDA阳性标记的皮质脊髓束再生通过脊髓损伤部位,特别是他克莫司组可延续至距损伤中心1.7 cm 。苏木精-伊红染色显示,细胞移植组与他克莫司组2周时坏死灶开始缩小,泡沫细胞减少。电镜结果显示,他克莫司组1周时即出现较正常的微丝和微管结构,8周时星形细胞、许旺细胞、髓鞘典型多见,神经轴突的终末有较多的兴奋性递质和不典型的轴树连接,出现较多的结构正常的髓鞘。说明损伤大鼠移植神经干细胞后联合应用他克莫司后可减轻早期的急性炎症反应,保证神经细胞的存活,具有神经保护和神经营养作用,可加快神经功能的恢复。     

Protein post-translational modifications after spinal cord injury

Deficits in intrinsic neuronal capacities in the spinal cord,a lack of growth support,and suppression of axonal outgrowth by inhibitory molecules mean that spinal cord injury almost always has devastating consequences.As such,one of the primary targets for the treatment of spinal cord injury is to develop strategies to antagonize extrinsic or intrinsic axonal growth-inhibitory factors or enhance the factors that support axonal growth.Among these factors,a series of individual protein level disorders have been identified during the generation of axons following spinal cord injury.Moreover,an increasing number of studies have indicated that post-translational modifications of these proteins have important implications for axonal growth.Some researchers have discovered a variety of post-translational modifications after spinal cord injury,such as tyrosination,acetylation,and phosphorylation.In this review,we reviewed the post-translational modifications for axonal growth,functional recovery,and neuropathic pain after spinal cord injury,a better understanding of which may elucidate the dynamic change of spinal cord injury-related molecules and facilitate the development of a new therapeutic strategy for spinal cord injury.