机构：[a]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China中美神经科学研究所首都医科大学宣武医院[b]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China[c]Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China[d]Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
Objective: Hypothermia has demonstrated neuroprotection following ischemia in preclinical studies while its clinical application is still very limited. The aim of this study was to explore whether combining local hypothermia in ischemic territory achieved by intra-arterial cold infusions (IACIs) with pharmacologically induced hypothermia enhances therapeutic outcomes, as well as the underlying mechanism. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h using intraluminal hollow filament. The ischemic rats were randomized to receive: 1) pharmacological hypothermia by intraperitoneal (i.p.) injection of dihydrocapsaicin (DHC); 2) physical hypothermia by IACIs for 10 min; or 3) the combined treatments. Extent of brain injury was determined by neurological deficit, infarct volume, and apoptotic cell death at 24 h and/or 7 d following reperfusion. ATP and ROS levels were measured. Expression of p-Akt, cleaved Caspase-3, pro-apoptotic (AIF, Bax) and antiapoptotic proteins (Bcl-2, Bcl-xL) was evaluated at 24 h. Finally, P131( inhibitor was used to determine the effect of p-Akt. Results: DHC or IACIs each exhibited hypothermic effect and neuroprotection in rat MCAO models. The combination of pharmacological and physical approaches led to a faster and sustained reduction in brain temperatures and improved ischemia-induced injury than either alone (P < 0.01). Furthermore, the combination treatment favorably increased the expression of anti-apoptotic proteins and decreased pro-apoptotic protein levels (P < 0.01 or 0.05). This neuroprotective effect was largely blocked by p-Akt inhibition, indicating a potential role of Akt pathway in this mechanism (P < 0.01 or 0.05). Conclusions: The combination approach is able to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection following ischemic stroke. The findings here move us a step closer towards translating this long recognized TH from bench to bedside. (C) 2017 Elsevier B.V. All rights reserved.
基金：
National Natural Science Foundation of China (81500997, 81371289);
National Natural Science Foundation of China for Outstanding Youth (81325007);
Chang Jiang Scholars Program (#T2014251) from the Chinese Ministry of Education;
Beijing Municipal Science and Technology Project (2121100005312016, D131100005313017);
National Science and Technology Support Plan Project (2013BAI07B01);
The "mission”talent project of Beijing Municipal Administration of Hospitals (SML20150802).
第一作者机构：[a]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China[b]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China[c]Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
通讯作者：
通讯机构：[*1]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
推荐引用方式(GB/T 7714)：
Di Wu,Jingfei Shi,Omar Elmadhoun,et al.Dihydrocapsaicin (DHC) enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat[J].BRAIN RESEARCH.2017,1671:18-25.doi:10.1016/j.brainres.2017.06.029.
APA：
Di Wu,Jingfei Shi,Omar Elmadhoun,Yunxia Duan,Hong An...&Yuchuan Ding.(2017).Dihydrocapsaicin (DHC) enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat.BRAIN RESEARCH,1671,
MLA：
Di Wu,et al."Dihydrocapsaicin (DHC) enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat".BRAIN RESEARCH 1671.(2017):18-25
