2-Cl-MGV-1 Ameliorates Apoptosis in the Thalamus and Hippocampus and Cognitive Deficits After Cortical Infarct in Rats
2-Cl-MGV-1 Ameliorates Apoptosis in the Thalamus and Hippocampus and Cognitive Deficits After Cortical Infarct in Rats
复制标题
2-Cl-MGV-1 改善大鼠丘脑和海马细胞凋亡以及皮质梗塞后的认知缺陷
DOI：
10.1161/strokeaha.117.019439
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发表时间：
2017-12-01
期刊：
影响因子：
8.3
通讯作者：
Gavish, Moshe
中科院分区：
文献类型：
--
作者：
Chen, Yicong;Veenman, Leo;Gavish, Moshe
背景和目的：局灶性皮质梗死引起同侧非缺血性丘脑和海马神经元凋亡，这可能与卒中后认知功能障碍有关。TSPO（translocator protein）在调节线粒体凋亡途径中起关键作用。我们研究了新的TSPO配体2-（2-氯苯基）喹唑啉-4-基二甲基氨基甲酸酯（2-氯-MGV-1）对中风后认知功能障碍，神经元线粒体凋亡，并在同侧丘脑和海马皮质infarct. Methods后继发性损害的影响，114只高血压大鼠进行了成功的远端大脑中动脉闭塞（n=76）或假手术（n=38）。在大脑中动脉远端闭塞后2小时给予2-Cl-MGV-1或二甲亚砜作为载体，然后持续6或13天（每组n=19）。Morris水迷宫检测大鼠空间学习记忆能力。使用尼氏染色，免疫组化，末端脱氧核苷酸转移酶dUTP缺口末端标记，JC-1染色，免疫印迹7和14天后surgical. Results-acetonatvolumes没有显着差异之间的车辆和2-氯-MGV-1组的丘脑和海马的继发变性和线粒体凋亡进行了评估。在大脑中动脉远端闭塞后7和14天，溶剂组的同侧丘脑和海马中有更多的神经元和更少的胶质细胞。与溶剂组相比，2-Cl-MGV-1可显著改善空间认知障碍，减少神经元死亡和胶质细胞活化（P
Background and Purpose-Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl) quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction.Methods-One hundred fourteen hypertensive rats underwent successful distal middle cerebral artery occlusion (n=76) or sham procedures (n=38). 2-Cl-MGV-1 or dimethyl sulfoxide as vehicle was administrated 2 hours after distal middle cerebral artery occlusion and then for 6 or 13 days (n=19 per group). Spatial learning and memory were tested using the Morris water maze. Secondary degeneration and mitochondrial apoptosis in the thalamus and hippocampus were assessed using Nissl staining, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling, JC-1 staining, and immunoblotting 7 and 14 days after surgery.Results-Infarct volumes did not significantly differ between the vehicle and 2-Cl-MGV-1 groups. There were more neurons and fewer glia in the ipsilateral thalamus and hippocampus in the vehicle groups than in the sham-operated group 7 and 14 days post-distal middle cerebral artery occlusion. 2-Cl-MGV-1 significantly ameliorated spatial cognitive impairment and decreased neuronal death and glial activation when compared with vehicle treatment (P