Mild hypothermia therapy attenuates early BBB leakage in acute ischemic stroke

Abstract

Reperfusion therapy inevitably leads to brain-blood barrier (BBB) disruption and promotes damage despite its benefits for acute ischaemic stroke (AIS). An effective brain cytoprotective treatment is still needed as an adjunct to reperfusion therapy. Here, we explore the potential benefits of therapeutic hypothermia (HT) in attenuating early BBB leakage and improving neurological outcomes. Mild HT was induced during the early and peri-recanalization stages in a mouse model of transient middle cerebral artery occlusion and reperfusion (tMCAO/R). The results showed that mild HT attenuated early BBB leakage in AIS, decreased the infarction volume, and improved functional outcomes. RNA sequencing data of the microvessels indicated that HT decreased the transcription of the actin polymerization-related pathway. We further discovered that HT attenuated the ROCK1/MLC pathway, leading to a decrease in the polymerization of G-actin to F-actin. Arachidonic acid (AA), a known structural ROCK agonist, partially counteracted the protective effects of HT in the tMCAO/R model. Our study highlights the importance of early vascular protection during reperfusion and provides a new strategy for attenuating early BBB leakage by HT treatment for ischaemic stroke.