Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system characterized by oligodendrocyte loss and progressive neurodegeneration. The cuprizone (CPZ)-induced demyelination is widely used to investigate the demyelination/remyelination. Here, we explored the therapeutic effects of Hydroxyfasudil (HF), an active metabolite of Fasudil, in CPZ model. HF improved behavioral abnormality and reduced myelin damage in the corpus callosum. Splenic atrophy and myelin oligodendrocyte glycoprotein (MOG) antibody were observed in CPZ model, which were partially restored and obviously inhibited by HF, therefore reducing pathogenic binding of MOG antibody to oligodendrocytes. HF inhibited the percentages of CD4+IL-17+ T cells from splenocytes and infiltration of CD4+ T cells and CD68+ macrophages in the brain. HF also declined microglia-mediated neuroinflammation, and promoted the production of astrocyte-derived brain derived neurotrophic factor (BDNF) and regeneration of NG2+ oligodendrocyte precursor cells. These results provide potent evidence for the therapeutic effects of HF in CPZ-induced demyelination.

中文翻译：

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羟基法舒地尔可通过抑制MOG抗体和小胶质细胞激活铜硅酮小鼠模型来减轻脱髓鞘作用。

多发性硬化症（MS）是中枢神经系统的一种免疫介导的脱髓鞘疾病，其特征是少突胶质细胞丢失和进行性神经变性。铜酮（CPZ）诱导的脱髓鞘作用广泛用于研究脱髓鞘作用/脱髓鞘作用。在这里，我们探讨了法舒地尔的一种活性代谢产物羟基法舒地尔（HF）在CPZ模型中的治疗作用。HF改善了行为异常并减少了call体中的髓磷脂损伤。在CPZ模型中观察到脾萎缩和髓鞘少突胶质糖蛋白（MOG）抗体，其被HF部分恢复并且明显被HF抑制，因此降低了MOG抗体与少突胶质细胞的致病性结合。HF抑制了脾细胞中CD4 + IL-17 + T细胞的百分比以及脑中CD4 + T细胞和CD68 +巨噬细胞的浸润。HF还减少了小胶质细胞介导的神经炎症，并促进了星形胶质细胞衍生的脑源性神经营养因子（BDNF）的产生和NG2 +少突胶质细胞前体细胞的再生。这些结果为HF在CPZ诱导的脱髓鞘中的治疗作用提供了有力的证据。