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在多发性硬化(MS)斑块的组成细胞类型中,星形胶质细胞被认为在其发病机理中起很小的作用。传统认为,星形胶质细胞间接导致瘢痕形成,在病变形成或修复中几乎不起作用。然而,近来对脱髓鞘性视神经脊髓炎(NMO)的高度关注发现,抗水通道蛋白-4的体液免疫反应引起的星形胶质细胞原发性损害,导致NMO首次被证实为髓鞘性疾病。NMO这一发现促使我们重新审视活动性损害的MS患者的数据和资料。我们的重新评估清楚显示血管周围星形胶质细胞终足和邻近脑实质星形胶质细胞的早期损伤,但难以评估这种损伤是否为急性损伤时伴发的脑水肿和炎症的主要原因。由于恢复中病灶显示髓鞘再生,以及覆盖在血管周围的星形胶质细胞的完整性存在缺陷,星形胶质细胞的损害持续时间长。本研究和相关文献均发现,星形胶质细胞在MS变化发展中所起复杂作用取决于病变时期和病变地形的变化。与星形胶质细胞的抑制性作用不同的是,越来越多的充足证据表明,星形胶质细胞积极参与病变的发展与修复。我们建议,因星形胶质细胞在MS病变中明确的早期选择性作用,星形胶质细胞也许可作为MS治疗的切入点。
In constitutive cell types of multiple sclerosis (MS) plaques, astrocytes are thought to play a minor role in their pathogenesis. Traditionally, astrocytes have been shown to cause scarring indirectly, with little or no effect on lesion formation or repair. However, a recent high focus on demyelinating optic neuromyelitis (NMO) has found that primary damage to astrocytes by the humoral immune response to aquaporin-4 leads to the first demonstration of NMO as myelin disease. The discovery of NMO prompted us to revisit the data and data of MS patients with active impairment. Our reevaluation clearly demonstrated perivascular astrocytes ending up with early damage to adjacent brain parenchymal astrocytes, but it was difficult to assess whether this injury was the major cause of brain edema and inflammation associated with acute injury. As the lesion in recovery shows remyelination and the integrity of the astrocytes covering the perivascular lining is defective, astrocyte damage lasts long. The present study and related literatures all found that the complex role of astrocytes in the development of MS depends on the lesion and the change of lesion topography. In contrast to the inhibitory effects of astrocytes, there is a growing body of evidence that astrocytes are actively involved in the development and repair of lesions. We suggest that astrocytes may be used as an entry point for MS treatment because of the clear early selectivity of astrocytes in MS lesions.