Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats
Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats
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DOI：
10.3109/08923973.2014.913616
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发表时间：
2014-06-01
影响因子：
3.3
通讯作者：
Xu, Chunsheng
中科院分区：
文献类型：
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作者：
Guo, Wei;Feng, Guoying;Xu, Chunsheng
脑水肿是脑缺血再灌注的主要后果。然而，很少有有效的治疗方案可用于延缓脑缺血后脑水肿的进展。最近，雷帕霉素已被证明在脑缺血再灌注后的大鼠中产生神经保护作用。雷帕霉素是否能减轻脑水肿损伤尚不清楚。在这项研究中，大鼠中风模型诱导1小时短暂的大脑中动脉闭塞使用管腔内细丝，然后再灌注48小时。雷帕霉素（250 μ g/kg体重，腹膜内; i. p.）对脑水肿进展的影响。结果显示，雷帕霉素治疗可显着减少脑梗死体积、脑组织含水量和伊文斯蓝透过血脑屏障（BBB）的渗出。雷帕霉素治疗可改善脑组织的组织学外观，增加毛细血管腔的空间，维持血脑屏障的完整性。雷帕霉素还抑制基质金属蛋白酶9（MMP 9）和水通道蛋白4（AQP 4）的表达。这些数据表明，雷帕霉素可以通过维持BBB的完整性和抑制MMP 9和AQP 4的表达来改善再灌注损伤后的脑水肿进展。本研究结果为雷帕霉素改善脑缺血再灌注后脑水肿提供了一种新的可能途径。
Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 mu g/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.