Rowland James W, Hawryluk Gregory W J, Kwon Brian, Fehlings Michael G
Division of Genetics and Development, Toronto Western Research Institute, Institute of Medical Science, University of Toronto, Canada.
Neurosurg Focus. 2008;25(5):E2. doi: 10.3171/FOC.2008.25.11.E2.
This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho-associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.
本综述总结了目前对脊髓损伤病理生理学的理解，并讨论了已转化为临床试验或极有可能转化为临床试验的重要新兴再生方法。脊髓损伤的病理生理学涉及直接破坏轴突、血管和细胞膜的原发性机械损伤。这种原发性机械损伤之后是继发性损伤阶段，包括血管功能障碍、水肿、缺血、兴奋性毒性、电解质紊乱、自由基产生、炎症和延迟性凋亡细胞死亡。损伤后，哺乳动物中枢神经系统由于中枢髓鞘和创伤后胶质瘢痕细胞外基质上表达的内在抑制因子而无法充分再生。阻断包括Nogo和Rho-Rho相关激酶途径在内的抑制信号的再生方法已显示出前景，正处于临床评估的早期阶段。基于细胞的策略，包括使用神经干细胞对残留轴突进行髓鞘再生，是一种有吸引力的新兴方法。
