Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis

Xiaoli Guo, Kazuaki Nakamura, Kuniko Kohyama, Chikako Harada, Heather A. Behanna, D. Martin Watterson, Yoh Matsumoto, Takayuki Harada*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Activated microglia and astrocytes have been implicated in the course of multiple sclerosis (MS) and its animal model: experimental autoimmune encephalomyelitis (EAE). MW01-5-188WH is a novel drug that selectively inhibits glial activation in the central nervous system (CNS). We report here that MW01-5-188WH is effective to ameliorate the severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Daily oral administration of MW01-5-188WH at 5 mg/kg body weight reduced the clinical scores of EAE mice while having no influence on the disease incidence or animal mortality. Pathological examination revealed reduced numbers of microglia and astrocytes in the spinal cord of MW01-5-188WH-treated EAE mice. Moreover, MW01-5-188WH suppressed the release of key chemokines, which are involved in MS pathology, from cultured microglia and astrocytes. Taken together, our results indicate that treatments that suppress the activation of microglia and astrocytes should be pursued in future research for their potential as avenues for the treatment of MS.

Original languageEnglish (US)
Pages (from-to)457-466
Number of pages10
JournalNeuroscience Research
Volume59
Issue number4
DOIs
StatePublished - Dec 1 2007

Keywords

  • Astrocytes
  • Chemokines
  • Experimental autoimmune encephalomyelitis
  • Glial activation
  • MW01-5-188WH
  • Microglia
  • Mouse
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

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