Retinoic acid ameliorates blood-brain barrier disruption following ischemic stroke in rats
Retinoic acid ameliorates blood-brain barrier disruption following ischemic stroke in rats
复制标题
视黄酸可改善大鼠缺血性中风后血脑屏障的破坏
DOI：
10.1016/j.phrs.2015.05.014
复制
发表时间：
2015-09-01
影响因子：
9.3
通讯作者：
Chen, Zhe-Yu
中科院分区：
文献类型：
--
作者：
Kong, Liang;Wang, Yue;Chen, Zhe-Yu
完整的血脑屏障（BBB）对于维持突触和神经元功能的稳定环境是必不可少的。在患者和动物模型中均观察到缺血和再灌注后BBB的破坏。视黄酸（RA）在脊椎动物器官发生过程中起重要作用，参与血脑屏障的发育。然而，目前尚不清楚RA是否可以预防缺血性卒中中的BBB破坏。在这项研究中，我们确定了连续4天注射RA导致闭合小带-1（ZO-1）和血管内皮钙粘蛋白（VE-钙粘蛋白）表达增加，这是BBB结构的重要组成部分。我们证明，RA预处理可以减轻缺血性脑卒中引起的血管通透性增加，这与ZO-1和VE-cadherin蛋白在大脑中动脉闭塞（MCAO）大鼠模型中的表达上调有关。我们的研究结果进一步证实，RA对BBB的保护作用依赖于RA受体和体外氧糖剥夺（OGD）处理。值得注意的是，MCAO后立即给予RA减少了组织纤溶酶原激活剂（tPA）诱导的脑出血（ICH），并改善了缺血性卒中后24小时的神经功能缺损。总之，我们的研究结果表明，RA可能成为一种新的治疗方法，以防止BBB功能障碍和tPA诱导的ICH缺血性卒中。(C)2015爱思唯尔有限公司版权所有。
The intact blood-brain barrier (BBB) is essential in maintaining a stabilized milieu for synaptic and neuronal functions. Disruptions of the BBB have been observed following ischemia and reperfusion, both in patients and in animal models. Retinoic acid (RA), which plays crucial roles during vertebrate organogenesis, has been reported to participate in BBB development. However, it remains unclear whether RA could prevent BBB disruption in ischemic stroke. In this study, we determined that the injection of RA for 4 consecutive days resulted in increases in zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) expression, which are crucial components of the BBB structure. We demonstrated that RA pretreatment could alleviate the ischemic stroke-induced enlargement of vascular permeability, which is related to the up-regulated expression of ZO-1 and VE-cadherin proteins in rat models of middle cerebral artery occlusion (MCAO). Our findings further corroborated that the RA protective effect on BBB is dependent on RA receptor a in vitro oxygen-glucose deprivation (OGD) treatment. Significantly, RA administration immediately after MCAO reduced tissue plasminogen activator (tPA)-induced intracerebral hemorrhage (ICH) and ameliorated neurological deficits 24h after ischemic stroke. Taken together, our results suggest that RA may become a new therapeutic approach to prevent BBB dysfunction and tPA-induced ICH in ischemic stroke. (C) 2015 Elsevier Ltd. All rights reserved.