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Enhanced oxidative stress response and neuroprotection of combined limb remote ischemic conditioning and atorvastatin after transient ischemic stroke in rats.

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机构: [1]Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China, [2]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China [3]Center of Stroke, Beijing Institute for Brain Disorder, Beijing, [4]Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA [5]Department of Endocrinology, Beijing, China,Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300, Jiangsu Province, China,
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关键词: Atorvastatin ischemia/reperfusion limb remote ischemic conditioning nuclear factor erythroid 2-related factor 2 pathway oxidative stress

摘要:
Limb remote ischemic conditioning (LRIC) and atorvastatin (AtS) both provide neuroprotection in stroke. We evaluated the enhanced neuroprotective effect of combining these two treatments in preventing ischemia/reperfusion (I/R)-induced cerebral injury in a rat model and investigated the corresponding molecular mechanisms. Transient cerebral ischemia was induced in Sprague-Dawley male rats by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion (I/R). Rats were divided into 5 groups, sham, I/R, I/R + AtS, I/R + LRIC and I/R + AtS + LRIC. Pretreatment with LRIC and/or AtS for 14 days before MCAO surgery. Infarct volume, neurological score, Western blot, immuno-histochemical analyses were performed. The combination of LRIC plus AtS pretreatment decreased infarct volume and inhibited neuronal apoptosis. Combination treatment achieved stronger neuroprotection than monotherapy with LRIC or AtS. These therapies reduced reactive oxygen species production in the peri-ischemia region, associated with significantly increased expression and activation of superoxide dismutase 1, hemeoxygenase 1 and nuclear factor erythroid 2-related factor 2. Both LRIC and AtS + LRIC treatments conferred neuroprotection in ischemic stroke by reducing brain oxidative stress. AtS plus LRIC is an attractive translational research option due to its ease of use, tolerability, economical, and tremendous neuroprotective potential in stroke.

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大类 | 4 区 医学
小类 | 4 区 临床神经病学 4 区 神经科学
第一作者:
第一作者机构: [1]Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China, [2]Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China [3]Center of Stroke, Beijing Institute for Brain Disorder, Beijing,
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通讯机构: [*1]Xuanwu Hospital, Capital Medical University
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