Protective effect of dexamethasone on osmotic-induced demyelination in rats.
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.
Sugimura
Yoshihisa
Y
Department of Teratology and Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Murase
Takashi
T
Takefuji
Seiko
S
Hayasaka
Shizu
S
Takagishi
Yoshiko
Y
Oiso
Yutaka
Y
Murata
Yoshiharu
Y
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006955:Hypernatremia / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D007010:Hyponatremia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D017590:Myelinolysis, Central Pontine / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000009:adverse effects*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D007074:Immunoglobulin G; D012462:Saline Solution, Hypertonic; D003907:Dexamethasone; D003894:Deamino Arginine Vasopressin