title: Evaluation of the protective potential of brain microvascular endothelial cell autophagy on blood-brain barrier integrity during experimental cerebral ischemia-reperfusion injury.
abstract: Brain microvascular endothelial cell (BMVEC) injury induced by ischemia-reperfusion (I/R) is the initial phase of blood-brain barrier (BBB) disruption, which results in a poor prognosis for ischemic stroke patients. Autophagy occurs in ischemic brain and has been shown to exhibit protective effects on endothelial cell against stress. However, the potential effects of BMVEC autophagy on BBB permeability during I/R and the mechanisms underlying these effects have yet to be elucidated. In the current study, we answered these questions by using chemical modulators of autophagy, including rapamycin and lithium carbonate acting, respectively, as mammalian target of rapamycin (mTOR)-dependent and mTOR-independent autophagy inducers and 3-methyladenine (3-MA) as an autophagy inhibitor. To mimic I/R injury, BMVECs were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), and a rat transient middle cerebral artery occlusion/reperfusion (MCAO/R) model was performed. All the drugs were given at 0.5 h before OGD/R or MCAO/R. First, enhancement of autophagy by rapamycin and lithium carbonate attenuated, whereas suppression of autophagy by 3-MA intensified BMVEC apoptosis and the high level of ROS induced by OGD/R. In addition, rapamycin and lithium carbonate pretreatments significantly reversed the decreased level of tight junction protein zonula occludens-1 (ZO-1) induced by OGD/R and promoted the distribution of ZO-1 on cell membranes. Finally, pretreatments with rapamycin and lithium carbonate reduced evans blue extravasation and brain water content in the ischemic hemisphere of the rat. In contrast, 3-MA pretreatment exerted opposite effects both in vitro and in vivo. These results may indicate a beneficial effect of BMVEC autophagy on BBB integrity during I/R injury.
authors: Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China.
authors: Haiying
authors: H
authors: Li
authors: Anju
authors: A
authors: Gao
authors: Dongxia
authors: D
authors: Feng
authors: Yang
authors: Y
authors: Wang
authors: Li
authors: L
authors: Zhang
authors: Yonghua
authors: Y
authors: Cui
authors: Bo
authors: B
authors: Li
authors: Zhong
authors: Z
authors: Wang
authors: Gang
authors: G
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002470:Cell Survival; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*