Fasudil Ameliorates disease Progression in Experimental Autoimmune Encephalomyelitis, Acting Possibly Through Antiinflammatory Effect.

Fasudil Ameliorates disease Progression in Experimental Autoimmune Encephalomyelitis, Acting Possibly Through Antiinflammatory Effect.

CNS Neurosci Ther. 2012 Sep 21;

Authors: Hou SW, Liu CY, Li YH, Yu JZ, Feng L, Liu YT, Guo MF, Xie Y, Meng J, Zhang HF, Xiao BG, Ma CG

Abstract
AIM: The purpose of this investigation was to further explore the mechanism(s) underlying the amelioration in EAE caused by Fasudil, particularly focusing on anti-inflammatory effect. METHODS: We induced a chronic-progressive experimental autoimmune encephalomyelitis (EAE) in B6 mice immunized with myelin oligodendrocyte glycoprotein(35-55) and performed Fasudil intervention in early and late stages of the disease. RESULTS: The administration of Fasudil (40�mg/kg, i.p) had a therapeutic effect in delaying the onset and ameliorating the severity of EAE, accompanied by the improvement in myelination and the decrease in inflammatory cells in spinal cords. Fasudil inhibited TLR-4, p-NF-kB/p65, and inflammatory cytokines (IL-1?, IL-6, and TNF-?) and enhanced IL-10 production in spinal cords. The ratio of arginase/iNOS was enhanced mainly in the spinal cords of EAE mice treated with Fasudil, reflecting a shift toward the M2 (antiinflammation) macrophage/microglia phenotype. The administration of Fasudil also induced the upregulation of CB2 receptor in spinal cords, but did not significantly trigger CB1 receptor. Levels of neurotrophic factors NGF, BDNF, and GDNF in the CNS were not altered by Fasudil. CONCLUSION: Fasudil ameliorates disease progression in EAE, acting possibly through antiinflammatory pathway.

PMID: 22994384 [PubMed - as supplied by publisher]

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