Time-dependent changes in proinflammatory and neurotrophic responses of microglia and astrocytes in a rat model of osmotic demyelination syndrome

Shintaro Iwama, Yoshihisa Sugimura, Haruyuki Suzuki, Hiromi Suzuki, Takashi Murase, Nobuaki Ozaki, Hiroshi Nagasaki, Hiroshi Arima, Yoshiharu Murata, Makoto Sawada, Yutaka Oiso

研究成果: Article

33 引用 (Scopus)

抜粋

Osmotic demyelination syndrome (ODS) is a serious demyelinating disease in the central nervous system usually caused by rapid correction of hyponatremia. In an animal model of ODS, we previously reported microglial accumulation expressing proinflammatory cytokines. Microglia and astrocytes secreting proinflammatory cytokines and neurotrophic factors are reported to be involved in the pathogenesis of demyelinative diseases. Therefore, to clarify the role of microglial and astrocytic function in ODS, we examined the time-dependent changes in distribution, morphology, proliferation, and mRNA/protein expression of proinflammatory cytokines, neurotrophic factors, and matrix metalloproteinase (MMP) in microglia and astrocytes 2 days (early phase) and 5 days (late phase) after the rapid correction of hyponatremia in ODS rats. The number of microglia time dependently increased at demyelinative lesion sites, proliferated, and expressed tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, inducible nitric oxide synthase, and MMP2, 9, and 12 at the early phase. Microglia also expressed leukemia inhibitory factor (a neurotrophic factor) and phagocytosed myelin debris at the late phase. The number of astrocytes time dependently increased around demyelinative lesions, extended processes to lesions, proliferated, and expressed nerve growth factor and glial cell line-derived neurotrophic factor at the late phase. Moreover, treatment with infliximab, a monoclonal antibody against TNF-α, significantly attenuated neurological impairments. Our results suggest that the role of microglia in ODS is time dependently shifted from detrimental to protective and that astrocytes play a protective role at the late phase. Modulation of excessive proinflammatory responses in microglia during the early phase after rapid correction may represent a therapeutic target for ODS.

元の言語English
ページ(範囲)452-462
ページ数11
ジャーナルGLIA
59
発行部数3
DOI
出版物ステータスPublished - 01-03-2011
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

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    Iwama, S., Sugimura, Y., Suzuki, H., Suzuki, H., Murase, T., Ozaki, N., Nagasaki, H., Arima, H., Murata, Y., Sawada, M., & Oiso, Y. (2011). Time-dependent changes in proinflammatory and neurotrophic responses of microglia and astrocytes in a rat model of osmotic demyelination syndrome. GLIA, 59(3), 452-462. https://doi.org/10.1002/glia.21114