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Therapeutic potential of experimental autoimmune encephalomyelitis by Fasudil, a Rho kinase inhibitor
Author(s) -
Yu JieZhong,
Ding Jing,
Ma CunGen,
Sun ChangHai,
Sun YiFu,
Lu ChuanZhen,
Xiao BaoGuo
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22339
Subject(s) - fasudil , experimental autoimmune encephalomyelitis , myelin oligodendrocyte glycoprotein , encephalomyelitis , rho associated protein kinase , rho kinase inhibitor , immunology , medicine , pathogenesis , immune system , biology , multiple sclerosis , microbiology and biotechnology , kinase
The migration of aberrant inflammatory cells into the central nervous system plays an important role in the pathogenesis of demyelinating diseases potentially through the Rho/Rho‐kinase (Rock) pathway, but direct evidence from human and animal models remains inadequate. Here we further confirm that Fasudil, a selective Rock inhibitor, has therapeutic potential in a mouse model of myelin oligodendrocyte glycoprotein (MOG)‐induced experimental autoimmune encephalomyelitis (EAE). The results show that Fasudil decreased the development of EAE in C57BL/6 mice. Immunohistochemistry disclosed that expression of Rock‐II in the perivascular spaces and vascular endothelial cells of spleens, spinal cords, and brains was elevated in EAE and was inhibited in the Fasudil‐treated group. T‐cell proliferation specific to MOG 35–55 was markedly reduced, together with a significant down‐regulation of interleukin (IL)‐17, IL‐6, and MCP‐1. In contrast, secretion of IL‐4 was increased, and IL‐10 was slightly elevated. There were no differences in the percentages of CD4 + CD25 + , CD8 + CD28 − , and CD8 + CD122 + in mononuclear cells. Histological staining disclosed a marked decrease of inflammatory cells in spinal cord and brain of Fasudil‐treated mice. These results, together with previous studies showing the inhibitory effect of Fasudil on T‐cell migration, might expand its clinical application as a new therapy for multiple sclerosis by decreasing cell migration and regulating immune balance. © 2010 Wiley‐Liss, Inc.