Ménard A, Amouri R, Dobránsky T, Charriaut-Marlangue C, Pierig R, Cifuentes-Diaz C, Ghandour S, Belliveau J, Gascan H, Hentati F, Lyon-Caen O, Perron H, Rieger F
INSERM, Laboratoire de Neuromodulations Interactives et Neuropathologies, Paris, France.
J Neurol Sci. 1998 Feb 5;154(2):209-21. doi: 10.1016/s0022-510x(97)00231-1.
The pathogenesis of multiple sclerosis (MS) is unknown. Searching for possible toxic factors, it was found that 3-day exposure to heat-treated cerebrospinal fluid (CSF) from MS patients caused apoptotic death of astrocytes and oligodendrocytes, but not fibroblasts, myoblasts, Schwann cells, endothelial cells and neurons, in vitro. CSFs from other inflammatory or non-inflammatory neurological diseases showed no toxicity. Exposure of these glial cells to partially purified MS CSF produced DNA fragmentation, apoptotic bodies, chromatin condensation, cell shrinkage, and changes in the levels of known cytokines. A cytotoxic factor, called gliotoxin, was characterized chromatographically as a stable 17-kDa glycoprotein. Since this protein is highly cytotoxic for astrocytes and oligodendrocytes, it may represent an initial pathogenic factor, leading to the neuropathological features of MS, such as blood-brain barrier involvement and demyelination.
多发性硬化症（MS）的发病机制尚不清楚。在寻找可能的毒性因素时，发现体外将星形胶质细胞和少突胶质细胞暴露于经热处理的MS患者脑脊液（CSF）3天会导致其凋亡死亡，但成纤维细胞、成肌细胞、施万细胞、内皮细胞和神经元则不会。来自其他炎性或非炎性神经疾病的CSF未显示出毒性。将这些神经胶质细胞暴露于部分纯化的MS CSF会导致DNA片段化、凋亡小体形成、染色质浓缩、细胞皱缩以及已知细胞因子水平的变化。一种名为神经毒素的细胞毒性因子经色谱分析鉴定为一种稳定的17 kDa糖蛋白。由于这种蛋白质对星形胶质细胞和少突胶质细胞具有高度细胞毒性，它可能代表了一种初始致病因素，导致了MS的神经病理学特征，如血脑屏障受累和脱髓鞘。
