ALDH2 Attenuates Blood-Brain Barrier Injury Induced by Cerebral Ischemia/Reperfusion via Alleviating ROS/NLRP3 Inflammasome Axis.

Abstract

An important factor influencing the prognosis of ischemic stroke is impairment of the blood-brain barrier (BBB). Additionally, oxidative stress and inflammation contribute significantly to the breakdown of the BBB during ischemic stroke reperfusion. Strong evidence suggested that Aldehyde dehydrogenase 2 (ALDH2) may have protective properties and reduce oxidative stress and inflammatory reactions in neurological conditions. Therefore, in order to examine the impact of ALDH2 on BBB integrity after ischemia/reperfusion (I/R) damage, we constructed the cerebral artery occlusion/reperfusion (MCAO/R) model and the oxygen-glucose deprivation/reperfusion (OGD/R) model. According to our findings, ALDH2 activation enhanced cell viability in bEnd.3 cells treated with OGD/R and reduced infarct area and neurological impairments in MCAO/R animals. Furthermore, both in vitro and in vivo, ALDH2 suppressed inflammation-related factors IL-1β and IL-18, as well as oxidative stress and the expression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome. In addition, bEnd.3 cells exhibited a reduced reactive oxygen species (ROS) generation function of ALDH2. Moreover, we noticed that ALDH2 boosted the expression of the tight junctions (TJs) zonula occludens-1 (ZO-1) and Occludin to control BBB function. In summary, ALDH2 protected against cerebral I/R injury and BBB destruction, and this protection was related to the ROS/NLRP3 axis.