Demyelination in multiple sclerosis.
Demyelination in multiple sclerosis.
复制标题
DOI：
10.1016/b978-0-444-52001-2.00004-2
复制
发表时间：
2014
影响因子：
--
通讯作者：
Stankoff B
中科院分区：
文献类型：
--
作者：
Lubetzki C;Stankoff B
这篇综述主要集中在多发性硬化的脱髓鞘，分为两部分。第一部分解决了许多而不是唯一的机制，导致在中枢神经系统脱髓鞘。尽管原发性少突胶质细胞或髓鞘损伤诱导中枢神经系统继发性免疫应答的假设仍存在争议，但最近的进展强调了针对髓鞘抗原的原发性免疫应答的影响，其具有多种潜在靶点。尽管多发性硬化长期以来被认为是一种T细胞介导的疾病，但B淋巴细胞的作用现在越来越被认识到，抗体对组织损伤的影响也在积极研究中。综述的第二部分描述了脱髓鞘的轴突后果。节段性脱髓鞘通过适应性反应导致传导阻滞或传导减慢，特别是与电压门控钠通道沿着裸露轴突分布的改变有关。如果脱髓鞘持续存在，这些变化以及营养和代谢支持的丧失将导致不可逆的轴突损伤和丧失。在这方面，有利于早期髓鞘修复，在轴突损伤仍然可逆的时间窗口期间，可能为神经保护铺平道路。
This review, focused on demyelination in multiple sclerosis, is divided in two parts. The first part addresses the many and not exclusive mechanisms leading to demyelination in the central nervous system. Although the hypothesis that a primary oligodendrocyte or myelin injury induces a secondary immune response in the central nervous system is still a matter of debate, most recent advances underline the influence of a primary immune response against myelin antigen(s), with a diversity of potential targets. Whereas multiple sclerosis was long considered as a T cell-mediated disease, the role of B lymphocytes is now increasingly recognized, and the influence of antibodies on tissue damage actively investigated. The second part of the review describes the axonal consequences of demyelination. Segmental demyelination results in conduction block or slowing of conduction through adaptative responses, notably related to modifications in the distribution of voltage gated sodium channels along the denuded axon. If demyelination persists, these changes, as well as the loss of trophic and metabolic support, will lead to irreversible axonal damage and loss. In this respect, favouring early myelin repair, during a window of time when axonal damage is still reversible, might pave the way for neuroprotection.