Combinatorial strategies with Schwann cell transplantation to improve repair of the injured spinal cord.
Combinatorial strategies with Schwann cell transplantation to improve repair of the injured spinal cord.
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DOI：
10.1016/j.neulet.2008.08.092
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发表时间：
2009-06-12
影响因子：
2.5
通讯作者：
Bunge MB
中科院分区：
文献类型：
--
作者：
Fortun J;Hill CE;Bunge MB
脊髓损伤（SCI）的直接影响是一种机械创伤，导致病变部位的直接损伤，随后是导致邻近神经元和胶质细胞损失的继发性反应。因此，SCI导致瘫痪和损伤水平以下的感觉丧失，自主神经反应改变，并且经常出现异常感觉和疼痛。当轴突开始发芽和细胞（包括炎症细胞、内皮细胞和雪旺细胞（SC））侵入损伤部位时，脊髓发生大量内源性重塑[6]，这可能有助于在人体中观察到的自发改善。尽管有这种内源性修复，但它是适度的，功能改善有限[47; 55]。由于治疗选择不足，需要额外的治疗干预。修复脊髓的一些策略集中在神经保护、再生和/或组织替代上。首先，应该设计策略来限制损伤对邻近轴突、神经元和神经胶质的二次扩散。第二，策略应该促进轴突重塑，以最大限度地发挥局部备用组织的功能。最后，需要通过减少抑制和/或提供允许的底物和营养分子来促进受损轴突长距离再生的策略。开发不同的损伤模型来模拟人类SCI的各个方面，以及现有的测试行为恢复的程序，显著提高了我们对SCI病理生理学的理解，重要的是，已经能够对无数的治疗干预进行调查。模型用于诱导完全或不完全SCI。标准化器械用于造成脊髓挫伤或压迫，导致不完全损伤，不同程度的保留取决于所用冲击的大小[4; 7; 24; 81]。由于损伤程度的标准化是这些模型的重要组成部分，因此对损伤参数和损伤后早期行为恢复的仔细检查是
The immediate effect of spinal cord injury (SCI) is a mechanical trauma that results in direct damage at the lesion site followed by secondary responses leading to loss of adjacent neurons and glia. Consequently, SCI leads to paralysis and loss of sensation below the level of the injury, altered autonomic responses and, frequently, the development of abnormal sensation and pain. Substantial endogenous remodeling of the spinal cord occurs [6] as axons begin to sprout and cells, including inflammatory, endothelial and Schwann cells (SCs), invade the injury site [34], likely contributing to spontaneous improvement observed in humans. Despite this endogenous repair, it is modest and functional improvements are limited [47; 55]. Because treatment options are inadequate, additional therapeutic interventions are needed. Some strategies to repair the spinal cord are focusing on neuroprotection, regeneration, and/or tissue replacement. First, strategies should be designed to limit the secondary spread of damage to adjacent axons, neurons and glia. Second, strategies should promote axonal remodeling to maximize the function of spared tissue locally. Lastly, strategies are needed to promote long distance regrowth of damaged axons by reducing inhibition and/or providing permissive substrates and trophic molecules.The development of different injury models to mimic various aspects of human SCI, together with existing procedures to test behavioral recovery, have improved significantly our understanding of the pathophysiology of SCI and, importantly, have enabled investigation of a myriad of therapeutic interventions. Models are utilized to induce complete or incomplete SCI. Standardized devices are used to produce contusion or compression of the spinal cord, resulting in incomplete injuries with varying degrees of sparing depending upon the magnitude of the impact used [4; 7; 24; 81]. Because standardization of the extent of injury is an essential component of these models, careful examination of the injury parameters and the behavioral recovery early after injury is