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Updated: Jul 18, 2026
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Role of microglia in the pathogenesis of osmotic-induced demyelination
Seiko Takefuji1, Takashi Murase, Yoshihisa Sugimura
1Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
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-alpha and IFN-gamma 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-alpha 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.
Insights
Microglia contribute to osmotic demyelination by releasing inflammatory cytokines. Lovastatin treatment reduced microglial activation and demyelination, suggesting a potential therapeutic strategy for this condition.
Area of Science:
- Neuroscience
- Pathology
Background:
- Osmotic demyelination, including central pontine myelinolysis, is a severe neurological condition.
- The role of microglia in the pathogenesis of osmotic demyelination is not fully understood.
Purpose of the Study:
- To investigate the role of microglia and their cytokine production in osmotic demyelination.
- To evaluate the therapeutic potential of lovastatin in a rat model of osmotic demyelination.
Main Methods:
- Osmotic demyelination was induced in rats via dDAVP infusion, liquid diet, and rapid correction of hyponatremia with hypertonic saline.
- Microglial accumulation and expression of TNF-alpha, IFN-gamma, and iNOS in demyelinated lesions were examined.
- Rats were treated with lovastatin to assess its effect on neurological deficits, demyelination, and microglial activity.
Main Results:
- Rats developed severe motor deficits and demyelination in the midbrain and cerebral cortex.
- Massive microglial accumulation expressing pro-inflammatory cytokines (TNF-alpha, IFN-gamma) and iNOS was observed in lesions.
- Lovastatin treatment significantly ameliorated neurological impairments and demyelination, reducing microglial accumulation and TNF-alpha expression.
Conclusions:
- Microglia play a detrimental role in osmotic demyelination pathogenesis through the production of pro-inflammatory cytokines.
- Lovastatin demonstrates potential as a therapeutic agent to mitigate demyelination by inhibiting microglial activation.
