Protective effect of dexamethasone on osmotic-induced demyelination in rats

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

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Abstract

Central pontine myelinolysis (CPM) is a serious demyelination disease commonly associated with the rapid correction of hyponatremia. Although its pathogenesis remains unclear, the disruption of the blood-brain barrier (BBB) as a consequence of a rapid increase in serum sodium concentration is considered to play a critical role. Since glucocorticoids are known to influence BBB permeability and prevent its disruption as a result of hypertension or hyperosmolarity, we investigated whether dexamethasone (DEX) could protect against osmotic demyelination in an animal model of CPM. Hyponatremia was induced in rats by liquid diet feeding and dDAVP infusion. Seven days later, the animals' hyponatremia was rapidly corrected by injecting a bolus of hypertonic saline intraperitoneally. Rats subjected to this treatment displayed serious neurological impairment and 77% died within 5 days of rapid correction of their hyponatremia; demyelinative lesions were observed in various brain regions in these animals. On the other hand, rats that were treated with DEX (2 mg/kg, 0 and 6 h after hypertonic saline injection) exhibited minimal neurological impairment and all were alive after 5 days. Demyelinative lesions were rarely seen in the brains of DEX-treated rats. A marked extravasation of endogenous IgG was observed in the demyelinative lesions in the brains of rats that did not receive DEX, indicating disruption of the BBB, but was not observed in DEX-treated rats. Furthermore, Evans blue injection revealed a significant reduction in staining in the brains of DEX-treated rats (P < 0.05). These results indicate that early DEX treatment can prevent the BBB disruption that is caused by the rapid correction of hyponatremia and its associative demyelinative changes, and suggest that DEX might be effective in preventing CPM.

Original languageEnglish
Pages (from-to)178-183
Number of pages6
JournalExperimental Neurology
Volume192
Issue number1
DOIs
Publication statusPublished - 03-2005

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

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    Sugimura, Y., Murase, T., Takefuji, S., Hayasaka, S., Takagishi, Y., Oiso, Y., & Murata, Y. (2005). Protective effect of dexamethasone on osmotic-induced demyelination in rats. Experimental Neurology, 192(1), 178-183. https://doi.org/10.1016/j.expneurol.2004.10.018