Ohlsson Marcus, Bellander Bo-Michael, Langmoen Iver A, Svensson Mikael
Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institutet and Hospital, 171-76 Stockholm, Sweden.
J Neurotrauma. 2003 Sep;20(9):895-904. doi: 10.1089/089771503322385827.
Activation of the complement cascade following peripheral nerve axotomy and following traumatic brain injury has been demonstrated in previous studies. This study investigates the temporal pattern of microglia/macrophages and complement activation following axotomy of sensory CNS neurons, using a standardized experimental crush injury of the optic nerve in adult rats. Numerous ED1-labeled macrophages were found at the lesion site and distal to the injury at 7 days post injury (dpi). Complement C3-mRNA was upregulated 2-28 days post lesion, indicating local synthesis of complement in the optic nerve. Furthermore, increased immunoreactivity (IR) for the end product of the complement cascade, the membrane attack complex (MAC), was detected along disintegrating axons co-labeled with anti-neurofilament distal to the injury. Double-labeling for microglia show MAC-immunoreactivity expressed in their immediate vicinity, indicating a key role of microglia/macrophages in complement activation. The complement regulator Clusterin was upregulated in astrocytes at the lesion site as well as in the distal portion of the injured optic nerve, suggesting activation of a defense response to endogenous complement attack. A crush injury of the optic nerve leads to complement activation at the site of lesion and along the distal portion of the nerve, as well as upregulation of the complement inhibitor Clusterin at least in astrocytes. Reactive microglial cells seem to have a key role in complement activation as a local source of C3. We suggest that the balance between complement activation and their regulators may have impact on axonal degeneration following optic nerve injury.
先前的研究已证实，外周神经轴突切断术后以及创伤性脑损伤后补体级联反应会被激活。本研究利用成年大鼠视神经标准化实验性挤压损伤，探究感觉中枢神经系统神经元轴突切断术后小胶质细胞/巨噬细胞的时间模式及补体激活情况。损伤后7天（dpi），在损伤部位及损伤远端发现大量ED1标记的巨噬细胞。损伤后2 - 28天，补体C3 - mRNA上调，表明视神经中补体的局部合成。此外，在损伤远端与抗神经丝蛋白共标记的崩解轴突上，检测到补体级联反应终产物膜攻击复合物（MAC）的免疫反应性增加。小胶质细胞双重标记显示MAC免疫反应性在其紧邻区域表达，表明小胶质细胞/巨噬细胞在补体激活中起关键作用。补体调节蛋白Clusterin在损伤部位的星形胶质细胞以及受损视神经远端部分上调，提示对内源性补体攻击的防御反应被激活。视神经挤压损伤导致损伤部位及神经远端补体激活，以及补体抑制剂Clusterin至少在星形胶质细胞中上调。反应性小胶质细胞似乎作为C3的局部来源在补体激活中起关键作用。我们认为补体激活与其调节因子之间的平衡可能对视神经损伤后的轴突退变有影响。
