Blood-brain barrier permeability change and regulation mechanism after subarachnoid hemorrhage
Blood-brain barrier permeability change and regulation mechanism after subarachnoid hemorrhage
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DOI：
10.1007/s11011-014-9609-1
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发表时间：
2015-04-01
影响因子：
3.6
通讯作者：
Xue, Yixue
中科院分区：
文献类型：
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作者：
Li, Zhiqing;Liang, Guobiao;Xue, Yixue
本研究旨在观察蛛网膜下腔出血（SAH）对血脑屏障（BBB）的影响，探讨SAH后急性脑损伤的分子机制。首次采用血管内细丝穿孔技术建立SD大鼠SAH模型。分别采用多普勒血流仪、伊文思蓝外渗法和透射电镜观察SAH后不同时间点局部脑血流量（rCBF）、血脑屏障通透性及脑组织超微结构的变化。免疫组化和Western blot检测Claudin-5、Occludin、Zo-1和Caveolin-1的表达变化。Western blot检测Akt、P-Akt和Foxo 1A的表达。血脑屏障通透性的变化在SAH后3和72 h出现两个高峰，与rCBF的变化相对应。SAH后BBB紧密连接开放，最大开放时间为3 h和72 h。SAH后Caveolin-1、Claudin-5和Akt表达无明显变化（P > 0.05），而Zo-1和Occludin表达明显下调（P < 0.05）。P-Akt在SAH后30 min表达明显降低，1、24 h表达明显升高，Foxo 1A在SAH后1、24 h表达明显上调（P < 0.05）。Zo-1和Occludin的下调以及Akt/FOXO信号通路可能参与了SAH后早期紧密连接开放和血脑屏障通透性的调节。
We aimed to investigate the blood brain barrier (BBB) change caused by subarachnoid hemorrhage (SAH) and to explore the molecular mechanisms of acute brain injury after SAH. The SD rat model of SAH was firstly established by endovascular filament perforation technique. The changes of regional cerebral blood flow (rCBF), BBB permeability and ultrastructure of brain tissue at different time points after SAH were respectively observed by Doppler flowmetry, evans blue extravasation and transmission electron microscopy. Meanwhile, the expression changes of Claudin-5, Occludin, Zo-1 and Caveolin-1 were detected by immunohistochemistry and Western blot. Furthermore, the expressions of Akt, P-Akt and Foxo1A were also measured by Western blot. The change of BBB permeability showed two peaks at 3 and 72 h after SAH, corresponding to the change of rCBF. The BBB tight junction opening can be observed after SAH, and the largest opening was occurred at 3 h and 72 h. There was no significant change in Caveolin-1, Claudin-5 and Akt expressions after SAH (P > 0.05), while Zo-1 and Occludin were significantly down-regulated (P < 0.05). The expression of P-Akt was obviously reduced at 30 min and then increased at 1 and 24 h, while Foxo1A was up-regulated at 1 and 24 h after SAH (P < 0.05). Down-regulated Zo-1 and Occludin, as well as Akt/FOXO signaling pathway may be involved in the regulation of tight junction opening and the BBB permeability in the early stage after SAH.