Neurovascular protection reduces early brain injury after subarachnoid hemorrhage
Neurovascular protection reduces early brain injury after subarachnoid hemorrhage
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DOI：
10.1161/01.str.0000141162.29864.e9
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发表时间：
2004-10-01
期刊：
影响因子：
8.3
通讯作者：
Zhang, JH
中科院分区：
文献类型：
--
作者：
Park, S;Yamaguchi, M;Zhang, JH
背景与目的：蛛网膜下腔出血(SAH)后脑组织发生细胞死亡，尤其是细胞凋亡。在建立的雄性SD大鼠血管内穿孔模型中，观察细胞凋亡与血脑屏障(BBB)破坏、脑水肿和死亡率的关系。方法：分别于SAH前1小时和SAH后6小时给予泛半胱氨酸天冬氨酸氨基转移酶抑制剂(z-VAD-FMK)。结果：细胞凋亡主要发生在脑组织内皮细胞，部分发生在海马神经元，大脑皮层的细胞凋亡程度较小。相应地，观察到SAH后24小时血脑屏障通透性和脑含水量增加，并伴有神经功能障碍和高死亡率。结论：z-VAD-FMK对SAH后早期脑损伤的保护作用可能与其对脑血管内皮细胞的神经血管保护作用有关。
Background and Purpose - Cell death, especially apoptosis, occurred in brain tissues after subarachnoid hemorrhage (SAH). We examined the relationships between apoptosis and the disruption of blood - brain barrier (BBB), brain edema, and mortality in an established endovascular perforation model in male Sprague-Dawley rats.Methods - A pan - caspase inhibitor (z-VAD-FMK) was administered intraperitoneally at 1 hour before and 6 hours after SAH. Expression of caspase-3 and positive TUNEL was examined as markers for apoptosis.Results - Apoptosis occurred mostly in cerebral endothelial cells, partially in neurons in the hippocampus, and to a lesser degree in the cerebral cortex. Accordingly, increased BBB permeability and brain water content were observed, accompanied by neurological deficit and a high mortality at 24 hours after SAH. z-VAD-FMK suppressed TUNEL and caspase-3 staining in endothelial cells, decreased caspase-3 activation, reduced BBB permeability, relieved vasospasm, abolished brain edema, and improved neurological outcome.Conclusions - The major effect of z-VAD-FMK on early brain injury after SAH was probably neurovascular protection of cerebral endothelial cells, which results in less damage on BBB.