Barnett M H, Henderson A P D, Prineas J W
Department of Medicine, University of Sydney, NSW, Australia.
Mult Scler. 2006 Apr;12(2):121-32. doi: 10.1191/135248506ms1304rr.
Advances in the neuropathology of multiple sclerosis (MS) have contributed greatly to our understanding of the mechanisms of tissue injury in the condition. Particular interest has focussed on the active MS lesion, defined by macrophage activity in the presence of partially demyelinated axons. This has led to the prevailing consensus that a T-cell dependent, macrophage-mediated, autoimmune attack on constituents in the normal myelin sheath underlies the disease. This hypothesis, which has been largely supported by comparisons with the animal model, experimental allergic encephalomyelitis, has recently been questioned by an analysis of the pathological events preceding myelin phagocytosis in nascent MS lesions. The prephagocytic changes in evolving lesions examined shortly after the onset of an MS relapse raise the possibility that oligodendrocyte cell death and associated changes within the myelin sheath initiate local macrophage scavenger activity, with subsequent amplification of the inflammatory response. The presence of such lesions in patients with a spectrum of pathological changes in nearby or distant active phagocytic plaques suggests that pathological heterogeneity in MS is largely due to evolution of lesional pathology, rather than pathogenic heterogeneity.
多发性硬化症（MS）神经病理学的进展极大地促进了我们对该病组织损伤机制的理解。特别令人关注的是活动性MS病灶，其定义为在部分脱髓鞘轴突存在的情况下巨噬细胞的活性。这导致了一种普遍的共识，即对正常髓鞘成分的T细胞依赖性、巨噬细胞介导的自身免疫攻击是该疾病的基础。这一假说在很大程度上得到了与动物模型实验性变应性脑脊髓炎比较的支持，但最近对新生MS病灶中髓鞘吞噬之前病理事件的分析对此提出了质疑。在MS复发开始后不久检查的正在演变的病灶中的吞噬前变化，增加了少突胶质细胞死亡和髓鞘内相关变化引发局部巨噬细胞清除活性，随后炎症反应放大的可能性。在附近或远处有活动性吞噬斑块的一系列病理变化的患者中存在此类病灶，表明MS中的病理异质性很大程度上是由于病灶病理的演变，而非致病异质性。
