title: Mild hypothermia alleviates brain oedema and blood-brain barrier disruption by attenuating tight junction and adherens junction breakdown in a swine model of cardiopulmonary resuscitation.
abstract: Mild hypothermia improves survival and neurological recovery after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). However, the mechanism underlying this phenomenon is not fully elucidated. The aim of this study was to determine whether mild hypothermia alleviates early blood-brain barrier (BBB) disruption. We investigated the effects of mild hypothermia on neurologic outcome, survival rate, brain water content, BBB permeability and changes in tight junctions (TJs) and adherens junctions (AJs) after CA and CPR. Pigs were subjected to 8 min of untreated ventricular fibrillation followed by CPR. Mild hypothermia (33°C) was intravascularly induced and maintained at this temperature for 12 h, followed by active rewarming. Mild hypothermia significantly reduced cortical water content, decreased BBB permeability and attenuated TJ ultrastructural and basement membrane breakdown in brain cortical microvessels. Mild hypothermia also attenuated the CPR-induced decreases in TJ (occludin, claudin-5, ZO-1) and AJ (VE-cadherin) protein and mRNA expression. Furthermore, mild hypothermia decreased the CA- and CPR-induced increases in matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression and increased angiogenin-1 (Ang-1) expression. Our findings suggest that mild hypothermia attenuates the CA- and resuscitation-induced early brain oedema and BBB disruption, and this improvement might be at least partially associated with attenuation of the breakdown of TJ and AJ, suppression of MMP-9 and VEGF expression, and upregulation of Ang-1 expression.
authors.affiliation: Beijing Key Laboratory of Cardiopulmonary-Cerebral Resuscitation, Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Jiebin
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Cardiopulmonary-Cerebral Resuscitation, Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Cardiopulmonary-Cerebral Resuscitation, Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Beijing Key Laboratory of Cardiopulmonary-Cerebral Resuscitation, Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Beijing FuXing Hospital, Capital Medical University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Cardiopulmonary-Cerebral Resuscitation, Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D001929:Brain Edema / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006323:Heart Arrest / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism; D013552:Swine; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D062507:Claudin-5; D020780:Matrix Metalloproteinase 9; D062793:Occludin; D012259:Ribonuclease, Pancreatic; D042461:Vascular Endothelial Growth Factor A; D062826:Zonula Occludens-1 Protein; D000099152:Cadherin 5; C046366:angiogenin