急性脊髓损伤修复的研究进展

脊髓损伤(spinal cord injury SCI)是一种常见而且严重的临床疾患。据统计发达国家的SCI发病率为28．3～45人／百万人／年，在美国每年有11000人遭此损伤；我国发病率虽较低，约6．7人／百万人／年，但每年也有1万余人遭此损伤，且以中青年胸腰段损伤最多。外伤性脊髓损伤修复的研究主要围绕     

微囊化异种雪旺细胞移植修复脊髓损伤的研究进展

轴突再生障碍是脊髓损伤(Spinal cord injury，SCI)导致永久性残疾的主要原因。研究发现，中枢神经系统(Central nervous system，CNS)的轴突再生障碍与其所处的抑制性胶质环境有关，如少突胶质细胞分泌的N1—35和N1—250(一种髓鞘相关阻断因子)、和MAG(髓鞘相关糖蛋白)，星形胶质细胞分     

中枢神经再生研究进展

中枢神经系统的神经元是一群高度分化的细胞,一旦损伤后其修复与再生是非常困难和复杂的.研究发现：中枢神经再生困难主要原因不是神经元本身,而是中枢神经系统微环境不适合神经元轴突再生[1].越来越多的研究表明：如果把受损中枢神经元置于合适的微环境中是可以再生的[2].目前促进神经修复与再生的策略主要是通过促进内在的再生能力和消除外在的抑制因素,改善其微环境.本文就目前对这一领域的研究进展做一简要的综述.     

神经干细胞移植及基因治疗:脊髓损伤修复的新策略

中枢神经系统损伤的治疗已成为世界各国神经科学家关注的焦点。自证实成年哺乳动物中枢神经系统存在有神经干细胞以来 ,各国学者致力于干细胞的分离、在神经丝裂原诱导下的增殖、通过基因转移技术获得永生化神经干细胞系等研究 ,并尝试用于中枢神经系统疾病的治疗。本文就脊髓损伤的神经干细胞移植以及神经干细胞作为载体对脊髓损伤进行基因治疗的现状及应用前景进行综述     

移植神经干细胞促进脊髓全横断大鼠结构与功能修复的研究

目的 探讨移植神经干细胞对脊髓全横断性大鼠部分结构与功能修复的影响。方法 在脊髓全横断处移植神经干细胞60d后，在横断处下方3mm注射荧光金逆行标记轴突再生的上运动神经元，用免疫组织化学检测神经干细胞在宿主内的分化，同时用体视学方法观测脑干红核和大脑皮质感觉运动区内锥体细胞层的神经元密度变化。用BBB评分法和爬网格法观测大鼠后肢运动功能的恢复等。结果 移植的神经干细胞能在宿主内存活并向前后方向迁移到脊髓内，部分神经干细胞分化为GFAP、NF-200和GAP-43阳性细胞。移植神经干细胞后在红核和感觉运动区内锥体细胞层可见有被荧光金标记的神经元胞体，脊髓横断处附近脊髓组织的溃变程度减轻，红核及躯体感觉运动区内神经元密度高于未移植组，大鼠后肢的自主运动功能明显好于未移植组。结论 神经干细胞移植入损伤脊髓后能分化为神经元及神经胶质细胞，能减轻脊髓的继发性损伤，保护受损伤的神经元，促进运动功能的恢复。     

硫酸软骨素蛋白聚糖与脊髓损伤轴突再生

脊髓损伤后传导束的纤维不能有效再生是脊髓损伤后修复与功能重建的难点之一,其中屏障之一是神经胶质瘢痕,主要由星形胶质细胞和硫酸软骨素蛋白聚糖（chondroitin sulfate proteoglycans,CSPGs）组成,轴突不能穿过神经胶质而再生,屏障导致营养不良,再生受阻。目前有关胶质瘢痕的形成过程与调控、CSPGs参与胶质瘢痕形成的机制、以及如何有效地控制瘢痕的形成从而促进轴突再生,仍存在许多未知领域。     

神经营养因子对脊髓损伤修复作用研究进展

脊髓损伤（SCI）是一种严重的神经系统创伤,后果严重常导致患者不同程度地瘫痪和大小便障碍,其致残率与耗费高给家庭及社会造成严重的负担.因此研究脊髓组织损伤后的再生和修复具有重要的现实意义.大量实验研究表明神经营养因子对脊髓损伤后的神经组织修复过程有重要作用.就这一领域新的研究进展作一综述.     

内皮祖细胞移植联合早期运动改善脊髓损伤区血管再生及后肢功能

BACKGROUND: Endothelial progenitor cells are widely used in the treatment of various vascular diseases, and early exercise training contributes to restore motor function after spinal cord injury. However, the therapeutic effects of endothelial progenitor cell transplantation or early exercise training alone are unfavorable. OBJECTIVE: To observe the influence of transplantation of endothelial progenitor cells combined with early exercise training on blood vessel regeneration and hind limb function in rats after spinal cord injury. METHODS: Eighty adult Sprague-Dawley rats were enrolled to establish spinal cord injury models using the modified Allen’s method, and then randomly divided into four groups. Rats were respectively given culture medium via the tail vein, injection of endothelial progenitor cells (3×106) via the tail vein, roller and treadmill trainings for 2 weeks, or injection of endothelial progenitor cells via the tail vein followed by 2 weeks of roller and treadmill trainings in the model, cell transplantation, exercise and combined groups. RESULTS AND CONCLUSION: At 2 weeks after transplantation, the hindlimb motor function of rats in the combined group was better than that in the cell transplantation group and exercise group, and moreover, the percentage of CM-Dil positive cells, the number of horseradish peroxidase-positive nerve fibers, capillary density and expression of vascular endothelial growth factor and brain-derived neurotrophic factor were also significantly higher in the combined group than the cell transplantation group and exercise group. These findings indicate that early exercise training has a neuroprotective role in spinal cord injury; endothelial progenitor cell transplantation combined with early exercise training can promote regeneration of synapses and blood vessels and improve hindlimb motor function of rats, probably by increasing expression levels of vascular endothelial growth factor and brain-derived neurotrophic factor.       

督脉电针与神经干细胞移植联合应用促进脊髓全横断大鼠受损伤的神经元存活及其轴突再生

目的探讨督脉电针与神经干细胞移植联合应用对脊髓全横断大鼠受损伤的神经元存活及其轴突再生的影响。方法将对照组、神经干细胞移植组、督脉电针组和督脉电针＋神经干细胞移植组的成年大鼠胸10脊髓段做全横断损伤;其中神经干细胞移植组和电针神经干细胞组在损伤处移植神经干细胞。电针组和电针神经干细胞移植组在术后开始接受督脉电针治疗。所有动物存活67d。结果1．电针神经干细胞移植组脊髓损伤处的去甲肾上腺素能、5-羟色胺受体、降钙素基因相关肽能和生长相关蛋白-43阳性染色的4种神经纤维均明显多于其他几组。2．电镜下可观察到脊髓横断处有再生的神经纤维穿越,在电针神经干细胞移植组尤为明显。3．大脑体感运动区皮质和中脑红核受损伤的神经元存活数量也多于其他几组,一些神经元的再生神经纤维可能穿越横断处,进入尾端脊髓组织。结论督脉电针与神经干细胞移植联合应用能促进脊髓全横断大鼠受损伤的神经元存活及其轴突再生。     

皮质脊髓束的发育和再生

皮质脊髓束(corticosp inal tract,CST)是脊髓中最重要的下行运动传导束,它的受损与临床上的中枢性硬瘫密切相关。CST神经元产生于大脑皮质ⅴ层,在发育过程中有轴突生长过剩及消除现象。不同物种之间CST纤维束生长的时间也不同。GAP-43、CNTF、GDNF等因子在CST的发育过程中起重要作用。CST损伤后,周围的微环境存在抑制性因素,导致其再生困难。目前的再生修复研究大多集中于神经或细胞移植、神经生长因子及抗抑制因子抗体的应用。     

Electroporation as a tool to study in vivo spinal cord regeneration.

Tailed amphibians such as axolotls and newts have the unique ability to fully regenerate a functional spinal cord throughout life. Where the cells come from and how they form the new structure is still poorly understood. Here, we describe the development of a technique that allows the visualization of cells in the living animal during spinal cord regeneration. A microelectrode needle is inserted into the lumen of the spinal cord and short rapid pulses are applied to transfer the plasmids encoding the green or red fluorescent proteins into ependymal cells close to the plane of amputation. The use of small, transparent axolotls permits imaging with epifluorescence and differential interference contrast microscopy to track the transfected cells as they contribute to the spinal cord. This technique promises to be useful in understanding how neural progenitors are recruited to the regenerating spinal cord and opens up the possibility of testing gene function during this process.     

胶质细胞移植治疗脊髓损伤的研究进展

脊髓损伤具有高发生率、高致残率、高生存率、高消耗、青壮年多发等特点。其相关治疗的研究主要是从挽救神经元的迟发型损害和死亡，促进神经元的再生和组织移植替代等方面进行。由于哺乳动物中枢神经系统损伤后期内源性修复能力有限，所以细胞移植可能是更为可行的修复途径。目前细胞移植分为神经干细胞移植、胶质细胞移植、基因修饰的细胞移植等。胶质细胞通过广泛分布的凸起构成神经组织的支架，对神经元胞体和突起有支持作用。出生后保持一定的分裂能力．受到创伤刺激时进行分裂增殖，形成胶质瘢痕。星形胶质细胞一方面位于神经细胞的附近．另一方面附着于毛细血管的终足。参与物质运输和血脑屏障的形成。此外，星形胶质细胞可能在神经元生成、突触网络形成、神经元电活动以及特异性神经系统疾病等过程中发挥着调控作用。基于上述理论．国内外进行了一系列胶质细胞移植修复脊髓损伤的实验研究．现就相关研究进展综述如下。     

壳聚糖材料在脊髓损伤后神经再生的研究与作用

背景：组织工程支架材料壳聚糖能复合多种种子细胞和神经因子,维持受损组织正常的解剖结构,防止胶质瘢痕挤压,对脊髓损伤后神经再生具有重要的意义。 目的：介绍壳聚糖材料在修复脊髓损伤后神经再生领域的研究现状。 方法：由第一作者检索1990至2012年 PubMed数据库、CNKI数据库及万方数据库有关壳聚糖材料特性、壳聚糖导管移植治疗脊髓损伤的相关文献。 结果与结论：壳聚糖具有良好的物理、化学性能,并且具有良好的生物相容性、生物降解性,免疫抗原性小和无毒性等特殊生物医学特性,与嗅鞘细胞、骨髓间充质干细胞及神经干细胞具有良好的亲和性。壳聚糖材料制备的神经导管、支架能在脊髓损伤后桥接神经断端,维持神经再生的正常解剖结构,提供种子细胞及细胞因子载体,为损伤后神经再生提供良好的微环境,但目前对于壳聚糖导管的研究仍不够全面,仍有很多问题待解决。     

Urodele spinal cord regeneration and related processes.

Urodele amphibians, newts and salamanders, can regenerate lesioned spinal cord at any stage of the life cycle and are the only tetrapod vertebrates that regenerate spinal cord completely as adults. The ependymal cells play a key role in this process in both gap replacement and caudal regeneration. The ependymal response helps to produce a different response to neural injury compared with mammalian neural injury. The regenerating urodele cord produces new neurons as well as supporting axonal regrowth. It is not yet clear to what extent urodele spinal cord regeneration recapitulates embryonic anteroposterior and dorsoventral patterning gene expression to achieve functional reconstruction. The source of axial patterning signals in regeneration would be substantially different from those in developing tissue, perhaps with signals propagated from the stump tissue. Examination of the effects of fibroblast growth factor and epidermal growth factor on ependymal cells in vivo and in vitro suggest a connection with neural stem cell behavior as described in developing and mature mammalian central nervous system. This review coordinates the urodele regeneration literature with axial patterning, stem cell, and neural injury literature from other systems to describe our current understanding and assess the gaps in our knowledge about urodele spinal cord regeneration.     

Multiple-channel scaffolds to promote spinal cord axon regeneration

As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic-co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments. Injection molding with rapid solvent evaporation resulted in scaffolds with a plurality of distinct channels running parallel along the length of the scaffolds. The feasibility of creating scaffolds with various channel sizes and geometries was demonstrated. Walls separating open channels were found to possess void fractions as high as 89%, with accessible void fractions as high as 90% through connections 220 microm or larger. Scaffolds degraded in vitro over a period of 30 weeks, over which time-sustained delivery of a surrogate drug was observed for 12 weeks. Primary neonatal Schwann cells were distributed in the channels of the scaffold and remained viable in tissue culture for at least 48 h. Schwann-cell containing scaffolds implanted into transected adult rat spinal cords contained regenerating axons at one month post-operation. Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections.     

Nerve regeneration in the dorsal funiculus of the rat spinal cord: a light and electron microscopic study

In an attempt to identify regenerating axons in the central nervous system, a partial transection of the dorsal funiculus in the rat spinal cord was carried out with a pair of microdissection scissors, and a nylon thread loop was inserted into the lesion to demarcate the severed tissue. Nerve regeneration through the demarcated lesion was observed 4-20 days after the operation by light and electron microscopy. In the early stage, many naked axons appeared from the caudal part of the lesion, and some of these further extended into the demarcated space. They contained an accumulation of mitochondria, smooth-surfaced endoplasmic reticulum and vesicles in the axoplasm; this axoplasmic feature indicated that they were regenerating axons. They gradually increased in number, and took highly irregular courses exhibiting various fluctuations in diameter throughout their lengths. Immature Schwann cells as well as glial cells including oligodendrocytes and astrocytes appeared in close association with these regenerating axons. Oligodendrocytes eventually formed thin myelin sheaths. On the other hand, naked axons were present deflecting outside the thread loop; they showed no axoplasmic characteristics as described above. These axons could be regarded as uninjured ones merely undergoing demyelination due to the surgery. Thus, regenerating axons were clearly distinguished from merely demyelinated ones, and some of them were shown to grow through the traumatic lesion in the dorsal funiculus of the rat spinal cord.