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O107 - FASUDIL EXERTS ANTI-INFLAMMATORY AND ENHANCES REMYELINATION THROUGH INDUCING ASTROCYTIC TRANSFORMATION TO A2 PHENOTYPE (ID 181)
Abstract
Background and Aims
Multiple sclerosis (MS) is mainly involved in neuroinflammation and demyelination of CNS, in which remyelination failure results in persistent neurological impairment. Fasudil has been shown to have beneficial effects in several models of neurological diseases. In this study, the therapeutic potential and possible mechanisms of Fasudil for remyelination were explored through modulation of astrocytic polarization in cell and animal models.
Methods
The effects of Fasudil on primary astrocytes induced by inflammatory factors were explored. Then these effects were further confirmed in CPZ-induced mice model. CPZ diet was prepared for C57BL/6 mice, which were divided into CPZ and Fasudil group. Fasudil (40 mg/kg/d) was injected intraperitoneally after fifth week of CPZ diet.
Results
Fasudil not only down-regulated the expression of C3 and CFB, but also up-regulated the expression of S100A10 and Ptx3 in inflammatory factor-induced astrocytes. Fasudil intervention lowered expression of inflammatory cytokines IL-6, TNF-α, and increased expression of anti-inflammatory cytokines IL-10, TGF-β in the supernatants of cultured astrocytes. Fasudil improved anxiety/depression-like behaviors and promoted the remyelination of CPZ mice through affecting the polarization of astrocytes. Meanwhile, Fasudil inhibited the expression of C3/CFB and increased the expression of S100A10/Ptx3 in CPZ-diet brain, promoting the expression of NG2.
Conclusions
Fasudil exerts anti-inflammation and enhances remyelination through inducing astrocytic transformation to A2 phenotype, indicating a potential approach for CPZ-induced demyelination. (Supported by NSF of China 81473577, China Postdoctoral Science Foundation 2020M680912, The Doctoral Research Start-up Fund of Shanxi Bethune Hospital 2021RC033. Ma and Xiao are corresponding authors).