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CD151 减轻大鼠实验性局灶性脑缺血后早期血脑屏障功能障碍。

CD151 Alleviates Early Blood-Brain Barrier Dysfunction After Experimental Focal Brain Ischemia in Rats.

机构信息

Department of Neurology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.

出版信息

Cell Mol Neurobiol. 2021 Jan;41(1):151-162. doi: 10.1007/s10571-020-00842-1. Epub 2020 Apr 13.

DOI:10.1007/s10571-020-00842-1
PMID:32285246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11448708/
Abstract

Preservation of the blood-brain barrier (BBB) function is a potential protective strategy against cerebral ischemic injuries. CD151 has a beneficial effect in maintaining vascular stability and plays a role in pro-angiogenesis. Both vascular stability and angiogenesis can affect BBB function. Therefore, we aimed to examine the action of CD151 in regulating BBB permeability after cerebral ischemic injury in the present study. Using a transient focal cerebral ischemia (tFCI) rat model, we established that CD151 overexpression in the brain mitigated the leakage of endogenous IgG at 6-24 h after tFCI in vivo. Moreover, we found that CD151 can decrease the diffusion of macromolecules through monolayer brain microvessel endothelial cells (BMVECs) after glucose and oxygen deprivation (OGD)-reoxygenation in vitro. Furthermore, overexpression of CD151 in BMVECs suppressed OGD-reoxygenation-induced F-actin formation and RhoA activity. However, while preserving BBB integrity after tFCI, CD151 overexpression did not affect the post-stroke outcomes. Taken together, the present study demonstrated that CD151 overexpression in the brain protects BBB permeability at early phase after tFCI. CD151 may be a potential target for early BBB protection in ischemic stroke.

摘要

保护血脑屏障(BBB)功能是防止脑缺血损伤的一种潜在保护策略。CD151 对维持血管稳定性具有有益作用,并在促进血管生成中发挥作用。血管稳定性和血管生成都可以影响 BBB 功能。因此,本研究旨在研究 CD151 在调节脑缺血损伤后 BBB 通透性中的作用。我们使用短暂性局灶性脑缺血(tFCI)大鼠模型,发现脑内 CD151 的过表达减轻了体内 tFCI 后 6-24 小时内内源性 IgG 的渗漏。此外,我们发现 CD151 可以减少体外葡萄糖和氧剥夺(OGD)-复氧后大分子通过单层脑微血管内皮细胞(BMVECs)的扩散。此外,CD151 在 BMVECs 中的过表达抑制了 OGD-复氧诱导的 F-肌动蛋白形成和 RhoA 活性。然而,尽管在 tFCI 后保持 BBB 完整性,CD151 的过表达并不影响中风后的结果。综上所述,本研究表明,脑内 CD151 的过表达可在 tFCI 后早期保护 BBB 的通透性。CD151 可能是缺血性中风早期 BBB 保护的潜在靶点。

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