Mechanisms and Therapy of Osmotic Demyelination

Murase, Takashi; Sugimura, Yoshihisa; Takefuji, Seiko; Oiso, Yutaka; Murata, Yoshiharu

doi:10.1016/j.amjmed.2006.05.010

« Previous Next »The American Journal of Medicine
Volume 119, Issue 7, Supplement 1 , Pages S69-S73, July 2006

Mechanisms and Therapy of Osmotic Demyelination

Takashi Murase, MD, PhD
- Department of Teratology and Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
- Requests for reprints should be addressed to Takashi Murase, MD, PhD, Department of Teratology and Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Yoshihisa Sugimura, MD
- Department of Teratology and Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
Seiko Takefuji, MD
- Department of Teratology and Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
- Department of Metabolic Diseases, Nagoya University Graduate School of Medicine, Nagoya, Japan
Yutaka Oiso, MD, PhD
- Department of Metabolic Diseases, Nagoya University Graduate School of Medicine, Nagoya, Japan
Yoshiharu Murata, MD, PhD
- Department of Teratology and Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan

Abstract

Central pontine myelinolysis (CPM) is a rare but serious demyelinative disease that is associated with rapid correction of chronic hyponatremia. Disruption of the blood-brain barrier (BBB) following a rapid increase in serum sodium concentration is considered to play a critical role in the pathogenesis of osmotic demyelination. We investigated the protective effect of dexamethasone (DEX) on osmotic demyelination in rats. After rapid correction of chronic hyponatremia, rats displayed serious neurologic impairments and demyelinative lesions were observed in various brain regions. Conversely, DEX-treated rats exhibited minimal neurologic impairments and demyelinative lesions were rarely seen in the brain. A marked extravasation of endogenous immunoglobulin G and Evans blue dye were observed in the brains of rats that did not receive DEX, indicating disruption of the BBB, but this was not observed in DEX-treated rats. These results indicate that DEX is effective in preventing osmotic demyelination by inhibiting BBB disruption, and suggest that DEX might be useful for the prevention of CPM in clinical practice.

Keywords: Blood-brain barrier , Central pontine myelinolysis , Demyelination , Dexamethasone , Hyponatremia