Effect of Fasudil on remyelination following cuprizone‐induced demyelination

• Published in: CNS neuroscience & therapeutics Vol. 26; no. 1; pp. 76 - 89
• Main Authors: Wang, Jing, Sui, Ruo‐Xuan, Miao, Qiang, Wang, Qing, Song, Li‐Juan, Yu, Jie‐Zhong, Li, Yan‐Hua, Xiao, Bao‐Guo, Ma, Cun‐Gen
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.01.2020
• Subjects: cuprizone‐induced demyelination; Fasudil; Original; remyelination; Rho kinase; Rho kinase; cuprizone-induced demyelination; Fasudil; remyelination
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.13154

Background Multiple sclerosis is characterized by demyelination/remyelination, neuroinflammation, and neurodegeneration. Cuprizone (CPZ)‐induced toxic demyelination is an experimental animal model commonly used to study demyelination and remyelination in the central nervous system. Fasudil is one of the most thoroughly studied Rho kinase inhibitors. Methods Following CPZ exposure, the degree of demyelination in the brain of male C57BL/6 mice was assessed by Luxol fast blue, Black Gold II, myelin basic protein immunofluorescent staining, and Western blot. The effect of Fasudil on behavioral change was determined using elevated plus maze test and pole test. The possible mechanisms of Fasudil action were examined by immunohistochemistry, flow cytometry, ELISA, and dot blot. Results Fasudil improved behavioral abnormalities, inhibited microglia‐mediated neuroinflammation, and promoted astrocyte‐derived nerve growth factor and ciliary neurotrophic factor, which should contribute to protection and regeneration of oligodendrocytes. In addition, Fasudil inhibited the production of myelin oligodendrocyte glycoprotein antibody and the infiltration of peripheral CD4+ T cells and CD68+ macrophages, which appears to be related to the integrity of the blood‐brain barrier. Conclusion These results provide evidence for the therapeutic potential of Fasudil in CPZ‐induced demyelination. However, how Fasudil acts on microglia, astrocytes, and immune cells remains to be further explored.