HSPB8-Mediated Actin Filament Reorganization by Promoting Autophagic Flux Confers Resilience to Blood-Brain Barrier (BBB) Injury in an In Vitro Model of Ischemic Stroke.

Abstract

Recently, uncontrolled actin polymerization has been recognized as an initiator of early-onset blood-brain barrier (BBB) rupture. Here, using in vitro models, we found that after oxygen-glucose deprivation/reperfusion (OGD/R), endothelial overexpression of HSPB8 suppressed aberrant actin polymerization and thus preserved the integrity of BBB. We further investigated the mechanisms of HSPB8 in the control of actin assembly. HSPB8 suppressed the RhoA/ROCK2/p-MLC signaling pathway in bEnd.3 cells and the RhoA activator abrogated the inhibitory action of HSPB8 on actin reorganization after OGD/R. In addition, endothelial autophagic flux was impaired after OGD/R. This effect was attenuated by HSPB8 overexpression. Autophagy inhibition partially reversed the effect of HSPB8 on the RhoA/ROCK2/p-MLC pathway. Taken together, the present study revealed that the restoration of autophagic flux by overexpressing HSPB8, via the inhibition of the RhoA/ROCK2/p-MLC signaling pathway, reverses the aggregation of endothelial cytoskeleton actin, eventually alleviating OGD/R-induced BBB injury.