PMID- 27235868 OWN - NLM STAT- MEDLINE DCOM- 20170622 LR - 20191210 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1646 DP - 2016 Sep 1 TI - Hypothermia-induced ischemic tolerance is associated with Drp1 inhibition in cerebral ischemia-reperfusion injury of mice. PG - 73-83 LID - S0006-8993(16)30404-8 [pii] LID - 10.1016/j.brainres.2016.05.042 [doi] AB - Excessive mitochondrial fission activation has been implicated in cerebral ischemia-reperfusion (IR) injury. Hypothermia is effective in preventing cerebral ischemic damage. However, effects of hypothermia on ischemia-induced mitochondrial fission activation is not well known. Therefore, the aim of this study was to investigate whether hypothermia protect the brain by inhibiting mitochondrial fission-related proteins activation following cerebral IR injury. Adult male C57BL/6 mice were subjected to transient forebrain ischemia induced by 15min of bilateral common carotid artery occlusion (BCCAO). Mice were divided into three groups (n=48 each): Hypothermia (HT) group, with mild hypothermia (32-34 degrees C) for 4h; Normothermia (NT) group, similarly as HT group except for cooling; Sham group, with vessels exposed but without occlusion or cooling. Hematoxylin and eosin (HE), Nissl staining, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and behavioral testing (n=6 each) demonstrated that hypothermia significantly decreased ischemia-induced neuronal injury. The expressions of Dynamin related protein 1 (Drp1) and Cytochrome C (Cyto C) (n=6 each) in mice hippocampus were measured at 3, 6, 24, and 72h of reperfusion. IR injury significantly increased expressions of total Drp1, phosphorylated Drp1 (P-Drp1 S616) and Cyto C under normothermia. However, mild hypothermia inhibited Drp1 activation and Cyto C cytosolic release, preserved neural cells integrity and reduced neuronal necrosis and apoptosis. These findings indicated that mild hypothermia-induced neuroprotective effects against ischemia-reperfusion injury is associated with suppressing mitochondrial fission-related proteins activation and apoptosis execution. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Tang, Yingying AU - Tang Y AD - Department of Anesthesiology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China; Department of Anesthesiology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Road 1, Hangzhou, Zhejiang 310006, China. FAU - Liu, Xiaojie AU - Liu X AD - Department of Anesthesiology, Qingdao Central Hospital, Shandong, China. FAU - Zhao, Jie AU - Zhao J AD - Department of Anesthesiology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China. FAU - Tan, Xueying AU - Tan X AD - Department of Hepatobiliary Surgery, Qingdao Municipal Hospital, Shandong, China. FAU - Liu, Bing AU - Liu B AD - Department of Anesthesiology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China. FAU - Zhang, Gaofeng AU - Zhang G AD - Department of Anesthesiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Shandong, China. FAU - Sun, Lixin AU - Sun L AD - Department of Anesthesiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Shandong, China. FAU - Han, Dengyang AU - Han D AD - Department of Anesthesiology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China. FAU - Chen, Huailong AU - Chen H AD - Department of Anesthesiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Shandong, China. Electronic address: chenhuailongdr@163.com. FAU - Wang, Mingshan AU - Wang M AD - Department of Anesthesiology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China; Department of Anesthesiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Shandong, China. Electronic address: wangmingshandr@163.com. LA - eng PT - Journal Article DEP - 20160526 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 9007-43-6 (Cytochromes c) RN - EC 3.6.5.5 (Dnm1l protein, mouse) RN - EC 3.6.5.5 (Dynamins) SB - IM MH - Animals MH - Apoptosis MH - Brain Ischemia/*metabolism/pathology/*therapy MH - Cytochromes c/metabolism MH - Dynamins/*metabolism MH - Hippocampus/metabolism/pathology MH - *Hypothermia, Induced MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mitochondria/*metabolism MH - *Mitochondrial Dynamics MH - Pyramidal Cells/pathology MH - Recognition, Psychology MH - Reperfusion Injury/pathology/therapy OTO - NOTNLM OT - Apoptosis OT - Drp1 OT - Hypothermia OT - Ischemia-reperfusion injury OT - Mitochondria fission EDAT- 2016/05/29 06:00 MHDA- 2017/06/24 06:00 CRDT- 2016/05/29 06:00 PHST- 2016/02/15 00:00 [received] PHST- 2016/04/22 00:00 [revised] PHST- 2016/05/24 00:00 [accepted] PHST- 2016/05/29 06:00 [entrez] PHST- 2016/05/29 06:00 [pubmed] PHST- 2017/06/24 06:00 [medline] AID - S0006-8993(16)30404-8 [pii] AID - 10.1016/j.brainres.2016.05.042 [doi] PST - ppublish SO - Brain Res. 2016 Sep 1;1646:73-83. doi: 10.1016/j.brainres.2016.05.042. Epub 2016 May 26.