Preventive and therapeutic effects of the selective Rho-kinase inhibitor fasudil on experimental autoimmune neuritis

Arnold Angelo M. Pineda, Motozumi Minohara, Nobutoshi Kawamura, Takuya Matsushita, Ryo Yamasaki, Xiaojia Sun, Hua Piao, Hiroaki Shimokawa, Jun Ichi Kira

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Abstract

We studied the effects of fasudil, a selective Rho-kinase inhibitor, on experimental autoimmune neuritis (EAN). Continuous parenteral administration of fasudil prevented the development of EAN induced by P0 peptide 180-199 in Lewis rats while it also reduced EAN severity when administered after disease onset. Immunohistochemical examination disclosed a marked decrease in the amount of inflammatory cell infiltration and attenuation of demyelination and axonal degeneration. Specific proliferation of lymphocytes from fasudil-treated rats in response to P0 peptide was significantly reduced as compared with those from phosphate-buffered saline (PBS)-treated rats. Fasudil treatment was associated with a significant reduction in secretion of IFN-γ; by contrast, secretion of IL-4 was almost the same in the fasudil- and PBS-treated groups. As a result, the IFN-γ/IL-4 ratio in the supernatant was significantly deceased in fasudil-treated rats compared with PBS-treated ones. Therefore, our results indicate a beneficial effect of selective blockade of Rho-kinase in animals with autoimmune inflammation of the peripheral nerves, and may provide a rationale for the selective blockade of Rho-kinase as a new therapy for Guillain-Barré syndrome.

Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalJournal of the Neurological Sciences
Volume306
Issue number1-2
DOIs
Publication statusPublished - Jul 15 2011

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All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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