Hagg Theo, Oudega Martin
Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery, University of Louisville, Louisville, Kentucky 40292, USA.
J Neurotrauma. 2006 Mar-Apr;23(3-4):264-80. doi: 10.1089/neu.2006.23.263.
Spinal cord injury results in acute as well as progressive secondary destruction of local and distant nervous tissue through a number of degenerative mechanisms. Spinal cord injury also initiates a number of endogenous neuroprotective and regenerative responses. Understanding of these mechanisms might identify potential targets for treatments after spinal cord injury in humans. Here, we first discuss recent developments in our understanding of the immediate traumatic and subsequent secondary degeneration of local tissue and long projecting pathways in animal models. These include the inflammatory and vascular responses during the acute phase, as well as cell death, demyelination and scar formation in the subacute and chronic phases. Secondly, we discuss the spontaneous axonal regeneration of injured and plasticity of uninjured systems, and other repair-related responses in animals, including the upregulation of regeneration-associated genes in some neurons, increases in neurotrophic factors in the spinal cord and remyelination by oligodendrocyte precursors and invading Schwann cells. Lastly, we comment on the still limited understanding of the neuropathology in humans, which is largely similar to that in rodents. However, there also are potentially important differences, including the reduced glial scarring, inflammation and demyelination, the increased Schwannosis and the protracted Wallerian degeneration in humans. The validity of current rodent models for human spinal cord injury is also discussed. The emphasis of this review is on the literature from 2002 to early 2005.
脊髓损伤会通过多种退行性机制导致局部和远处神经组织的急性以及进行性继发性破坏。脊髓损伤还会引发一系列内源性神经保护和再生反应。了解这些机制可能会为人类脊髓损伤后的治疗确定潜在靶点。在此，我们首先讨论在动物模型中对局部组织和长投射通路的直接创伤及随后继发性变性的最新认识进展。这些包括急性期的炎症和血管反应，以及亚急性期和慢性期的细胞死亡、脱髓鞘和瘢痕形成。其次，我们讨论动物中损伤轴突的自发再生和未损伤系统的可塑性，以及其他与修复相关的反应，包括一些神经元中再生相关基因的上调、脊髓中神经营养因子的增加以及少突胶质前体细胞和侵入的施万细胞的髓鞘再生。最后，我们评论一下目前对人类神经病理学的认识仍然有限，其在很大程度上与啮齿动物相似。然而，也存在潜在的重要差异，包括人类中胶质瘢痕形成、炎症和脱髓鞘减少，施万细胞增生增加以及华勒氏变性延长。还讨论了当前啮齿动物模型对人类脊髓损伤的有效性。本综述重点关注2002年至2005年初的文献。
