机构：[1]Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China神经科系统科技平台神经内科中美神经科学研究所首都医科大学宣武医院[2]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China[3]Center of Stroke, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China[4]Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China
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.
基金：
National Natural Science Foundation of China [82027802, 82071466, 82371470, 81771260, 82071468, 82201618]; Sail Plan Key Medical Specialty grant [ZYLX202139]; Mission talent project of Beijing Municipal Administration of Hospitals grant [SML20150802]; Beijing Municipal Science and Technology Project [Z181100001918026]; Science and Technology Innovation Service Capacity Building Project of Beijing Municipal Education Commission [11000023T000002157177]
第一作者机构：[1]Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China[2]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China
通讯作者：
通讯机构：[1]Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China[2]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China[3]Center of Stroke, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China[*1]Xuanwu Hospital, No. 45, Changchun Street, Xuanwu Hospital, Beijing 100053, China[*2]Xuanwu Hospital, 45 Changchun St., Beijing 100053, China
推荐引用方式(GB/T 7714)：
Yi Xu,Yunxia Duan,Shuaili Xu,et al.Mild hypothermia therapy attenuates early BBB leakage in acute ischaemic stroke[J].JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM.2024,doi:10.1177/0271678X241275761.
APA：
Yi Xu,Yunxia Duan,Shuaili Xu,Xiaoduo He,Jiaqi Guo...&Di Wu.(2024).Mild hypothermia therapy attenuates early BBB leakage in acute ischaemic stroke.JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM,,
MLA：
Yi Xu,et al."Mild hypothermia therapy attenuates early BBB leakage in acute ischaemic stroke".JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM .(2024)
医学