title: Fasudil ameliorates disease progression in experimental autoimmune encephalomyelitis, acting possibly through antiinflammatory effect.
abstract: OBJECTIVE
  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-1β, IL-6, and TNF-α) 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.
  
  
  CONCLUSIONS
  Fasudil ameliorates disease progression in EAE, acting possibly through antiinflammatory pathway.
authors.affiliation: Department of Neurology, Medical School, Institute of Brain Science, Shanxi Datong University, Datong, China.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Hou
authors.forename: Chun-Yun
authors.initials: CY
authors.lastname: Liu
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Li
authors.forename: Jie-Zhong
authors.initials: JZ
authors.lastname: Yu
authors.forename: Ling
authors.initials: L
authors.lastname: Feng
authors.forename: Yue-Ting
authors.initials: YT
authors.lastname: Liu
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Guo
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.forename: Jian
authors.initials: J
authors.lastname: Meng
authors.forename: Hai-Fei
authors.initials: HF
authors.lastname: Zhang
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Xiao
authors.forename: Cun-Gen
authors.initials: CG
authors.lastname: Ma
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil