机构：[1]China–America Joint Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.首都医科大学宣武医院[2]Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.[3]Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China.首都医科大学?脑血管病研究所首都医科大学宣武医院[4]Department of Neurosurgery, Beijing Tongren Hospital, Capital University of Medical Sciences, Beijing, China.[5]Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, China.神经外科首都医科大学宣武医院
Mild therapeutic hypothermia, a robust neuroprotectant, reduces neuronal apoptosis, but the precise mechanism is not well understood. Our previous study showed that a novel inhibitor of an apoptosis-stimulating protein of p53 (iASPP) might be involved in neuronal death after stroke. The aim of this study was to confirm the role of iASPP after stroke treated with mild therapeutic hypothermia. To address this, we mimicked ischemia/reperfusion injury in vitro by using oxygen-glucose deprivation/reperfusion (OGD/R) in primary rat neurons. In our in vivo approach, we induced middle cerebral artery occlusion (MCAO) for 60 min in C57/B6 mice. From the beginning of ischemia, focal mild hypothermia was applied for two hours. To evaluate the role of iASPP, small interfering RNA (siRNA) was injected intracerebroventricularly. Our results showed that mild therapeutic hypothermia increased the expression of iASPP and decreased the expression of its targets, Puma and Bax, and an apoptosis marker, cleaved caspase-3, in primary neurons under OGD/R. Increased iASPP expression and decreased ASPP1/2 expression were observed under hypothermia treatment in MCAO mice. iASPP siRNA (iASPPi) or hypothermia plus iASPPi application increased infarct volume, apoptosis and aggravated the neurological deficits in MCAO mice. Furthermore, iASPPi downregulated iASPP expression, and upregulated the expression of proapoptotic effectors, Puma, Bax and cleaved caspase-3, in mice after stroke treated with mild therapeutic hypothermia. In conclusion, mild therapeutic hypothermia protects against ischemia/reperfusion brain injury in mice by upregulating iASPP and thus attenuating apoptosis. iASPP may be a potential target in the therapy of stroke.
基金：
the National Natural Science Foundation of China (Grant no. 81471209, 81641055, 81000504, 81171241),
Beijing Natural Science Foundation (Grant no. 7132112),
the National Natural Science Foundation for Distinguished Young Scholars (Grant no. 81325007),
the Beijing Municipal Administration of Hospitals' Mission Plan (Grant no. SML20150802).
第一作者机构：[1]China–America Joint Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.[2]Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.[3]Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China.
通讯作者：
通讯机构：[*1]Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, China 100053,
推荐引用方式(GB/T 7714)：
Xiangrong Liu,Shaohong Wen,Shunying Zhao,et al.Mild Therapeutic Hypothermia Protects the Brain from Ischemia/Reperfusion Injury through Upregulation of iASPP[J].AGING AND DISEASE.2018,9(3):401-411.doi:10.14336/AD.2017.0703.
APA：
Xiangrong Liu,Shaohong Wen,Shunying Zhao,Feng Yan,Shangfeng Zhao...&Xunming Ji.(2018).Mild Therapeutic Hypothermia Protects the Brain from Ischemia/Reperfusion Injury through Upregulation of iASPP.AGING AND DISEASE,9,(3)
MLA：
Xiangrong Liu,et al."Mild Therapeutic Hypothermia Protects the Brain from Ischemia/Reperfusion Injury through Upregulation of iASPP".AGING AND DISEASE 9..3(2018):401-411
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