Role of microglia in the pathogenesis of osmotic-induced demyelination

Seiko Takefuji, Takashi Murase, Yoshihisa Sugimura, Yoshiko Takagishi, Shizu Hayasaka, Yutaka Oiso, Yoshiharu Murata

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30 Citations (Scopus)

Abstract

Osmotic demyelination is a serious disease caused by rapid correction of hyponatremia. In humans, demyelinative lesions occur preferentially in the central pons, and thus are termed central pontine myelinolysis. Although accumulation of microglia has been reported in such demyelinative lesions, their role in the pathogenesis of osmotic demyelination remains unclear. We examined the expression of cytokines in microglia that accumulated in the demyelinative lesions in a rat model of osmotic demyelination. Hyponatremia was induced in rats by a combination of dDAVP infusion and liquid diet feeding. After 7 days, serum sodium levels were rapidly corrected by hypertonic saline injection. The rats developed severe motor deficits, and marked demyelinative lesions were found in the midbrain and cerebral cortex. In the area of the demyelinative lesions, massive accumulations of microglia were observed that expressed the proinflammatory cytokines TNF-α and IFN-γ as well as iNOS. In contrast, in hyponatremia corrected rats treated with lovastatin, which is known to inhibit microglial infiltration in various animal models of CNS disease, neurological impairments and the degree of demyelination were significantly ameliorated. Lovastatin also reduced the accumulation of microglia and decreased the expression of TNF-α in the demyelinative lesions. These results indicate that microglia play a detrimental role in the pathogenesis of osmotic demyelination by producing proinflammatory cytokines, and further suggest that lovastatin may be useful in repressing the demyelination.

Original languageEnglish
Pages (from-to)88-94
Number of pages7
JournalExperimental Neurology
Volume204
Issue number1
DOIs
Publication statusPublished - 01-03-2007

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Microglia
Demyelinating Diseases
Lovastatin
Hyponatremia
Cytokines
Central Pontine Myelinolysis
Pons
Central Nervous System Diseases
Mesencephalon
Cerebral Cortex
Animal Models
Sodium
Diet
Injections
Serum

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Neurology

Cite this

Takefuji, S., Murase, T., Sugimura, Y., Takagishi, Y., Hayasaka, S., Oiso, Y., & Murata, Y. (2007). Role of microglia in the pathogenesis of osmotic-induced demyelination. Experimental Neurology, 204(1), 88-94. https://doi.org/10.1016/j.expneurol.2006.09.025
Takefuji, Seiko ; Murase, Takashi ; Sugimura, Yoshihisa ; Takagishi, Yoshiko ; Hayasaka, Shizu ; Oiso, Yutaka ; Murata, Yoshiharu. / Role of microglia in the pathogenesis of osmotic-induced demyelination. In: Experimental Neurology. 2007 ; Vol. 204, No. 1. pp. 88-94.
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Takefuji, S, Murase, T, Sugimura, Y, Takagishi, Y, Hayasaka, S, Oiso, Y & Murata, Y 2007, 'Role of microglia in the pathogenesis of osmotic-induced demyelination', Experimental Neurology, vol. 204, no. 1, pp. 88-94. https://doi.org/10.1016/j.expneurol.2006.09.025

Role of microglia in the pathogenesis of osmotic-induced demyelination. / Takefuji, Seiko; Murase, Takashi; Sugimura, Yoshihisa; Takagishi, Yoshiko; Hayasaka, Shizu; Oiso, Yutaka; Murata, Yoshiharu.

In: Experimental Neurology, Vol. 204, No. 1, 01.03.2007, p. 88-94.

Research output: Contribution to journalArticle

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AU - Takefuji, Seiko

AU - Murase, Takashi

AU - Sugimura, Yoshihisa

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