Protective effect of dexamethasone on osmotic-induced demyelination in rats
Protective effect of dexamethasone on osmotic-induced demyelination in rats
复制标题
DOI：
10.1016/j.expneurol.2004.10.018
复制
发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Murata, Y
中科院分区：
文献类型：
--
作者：
Sugimura, Y;Murase, T;Murata, Y
脑桥中央髓鞘溶解症(CPM)是一种严重的脱髓鞘疾病，通常伴随着低钠血症的迅速纠正。尽管其发病机制尚不清楚，但血脑屏障(BBB)的破坏被认为是血钠浓度快速升高的重要原因。由于糖皮质激素可影响血脑屏障通透性并防止高血压或高渗所致的血脑屏障破坏，我们在CPM动物模型上研究了地塞米松(DEX)对渗透性脱髓鞘的保护作用。采用流食加DDAVP灌胃诱导大鼠低钠血症。七天后，动物的低钠血症通过向腹膜内注射一团高渗盐水迅速得到纠正。接受这种治疗的大鼠表现出严重的神经功能障碍，77%的大鼠在低钠血症迅速纠正后5天内死亡；这些动物的不同脑区观察到脱髓鞘损害。而注射地塞米松(2 mg/kg，注射高渗盐水后0和6h)的大鼠神经功能损害轻微，5d后全部存活。地塞米松组大鼠脑内极少见脱髓鞘病变。未接受地塞米松治疗的大鼠，脑内脱髓鞘病变内可见明显的内源性免疫球蛋白外渗，提示血脑屏障的破坏，而给予地塞米松治疗的大鼠未观察到内源性免疫球蛋白的外渗。此外，伊文思蓝注射显示地塞米松处理组大鼠脑内染色显著减少(P<；0.05)。提示早期地塞米松治疗可防止低钠血症迅速纠正所致的血脑屏障紊乱及其相关的脱髓鞘改变，提示地塞米松可能是预防慢性髓鞘损伤的有效药物。(C)2004 Elsevier Inc.保留所有权利。
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. (C) 2004 Elsevier Inc. All rights reserved.