Linker Ralf A, Sendtner Michael, Gold Ralf
Department of Neurology, Clinical Research Group for Multiple Sclerosis, University of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
J Neurol Sci. 2005 Jun 15;233(1-2):167-72. doi: 10.1016/j.jns.2005.03.021. Epub 2005 Apr 21.
The major pathological hallmarks of multiple sclerosis (MS) comprise inflammation, demyelination with associated gliosis and axonal damage, which most likely correlates with persisting disability. Axonal damage can occur by several mechanisms. This article focuses on myelin disintegration and direct immune attack on axons by CD8-positive T-cells as two possible scenarios for axonal injury. As protoypic models, we investigated experimental autoimmune encephalomyelitis (EAE) in ciliary neurotrophic factor gene knockout mice (CNTF-/- mice) with severe myelin pathology and EAE in beta-2 microglobulin gene knockout mice (beta2m-/- mice) lacking CD8-positive T-cells. The results from these studies indicate that the trigger attack for axonal injury even in a well-defined experimental design can be multi-faceted. No single factor seems to be absolutely necessary for the initiation of the process, but they rather act in concert and orchestrate tissue destruction, inflammation and regeneration. Some mechanisms of primary or secondary axonal damage may be shared between inflammatory and degenerative diseases of the nervous system, thereby establishing a link which might be of importance for future therapeutic strategies.
多发性硬化症（MS）的主要病理特征包括炎症、伴有相关胶质细胞增生的脱髓鞘以及轴突损伤，而轴突损伤很可能与持续性残疾相关。轴突损伤可通过多种机制发生。本文重点探讨髓鞘崩解和CD8阳性T细胞对轴突的直接免疫攻击这两种可能导致轴突损伤的情况。作为典型模型，我们研究了患有严重髓鞘病理改变的睫状神经营养因子基因敲除小鼠（CNTF-/-小鼠）的实验性自身免疫性脑脊髓炎（EAE），以及缺乏CD8阳性T细胞的β2微球蛋白基因敲除小鼠（β2m-/-小鼠）的EAE。这些研究结果表明，即使在明确的实验设计中，轴突损伤的触发攻击也可能是多方面的。启动这一过程似乎并非绝对需要单一因素，而是多种因素协同作用，共同导致组织破坏、炎症和再生。原发性或继发性轴突损伤的一些机制可能在神经系统的炎症性和退行性疾病中共同存在，从而建立起一种联系，这可能对未来的治疗策略具有重要意义。
