• Chuan-Fang Wang, Cheng-Cheng Zhao, Yi He, Zong-Yang Li, Wen-Lan Liu, Xian-Jian Huang, Yue-Fei Deng, and Wei-Ping Li.
• Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
• Brain Behav. 2019 Apr 1; 9 (4): e01248.

BackgroundMild hypothermia is wildly used in clinical treatment of traumatic brain injury (TBI). However, the effect of mild hypothermia on endoplasmic reticulum (ER) stress-induced apoptosis after severe TBI is still unknown.MethodsIn the present study, we used BALB/c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing ER stress. Severe TBI was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4 hr. The animals were euthanized at 1 and 7 days after severe TBI. The expression levels of ER stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by TUNEL staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze.ResultsOur results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p-eIF2α/eIF2α, ATF4, CHOP and IRE-1α, and reduced apoptosis rate in the pericontusion region at 1 and 7 days after severe TBI. Interestingly, mild hypothermia also prevented the translocation of CHOP into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI.ConclusionsOur findings illustrated that mild hypothermia could reduce ER stress-induced apoptosis and improve neuronal functions after severe traumatic brain injury.© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

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