胆碱能信号调节脑梗死后自体神经干细胞分化

摘要

目的 探讨胆碱能信号对内源性神经干细胞(NSC)在脑梗死周围区分化的调节.方法 将小鼠随机分为假手术+溶剂组、脑梗死+溶剂组、脑梗死+多奈哌齐组、脑梗死+阿托品组,每组25只.线栓法建立大脑中动脉闭塞(MCAO)模型.术后1、7、14、21 d进行神经功能缺损评分,第3天测脑含水量,第14、28天免疫荧光观察梗死周围区或相应位置NeuN/BrdU、CNPase/BrdU、GFAP/BrdU阳性细胞数.结果 小鼠脑梗死后脑含水量增高(P<0.05),多奈哌齐处理可降低其脑含水量和神经功能缺损评分(P<0.05);梗死后梗死周围区NeuN/BrdU、CNPase/BrdU、GFAP/BrdU阳性细胞增多(P<0.05);对比脑梗死+溶剂组、脑梗死+多奈哌齐组NeuN/BrdU、CNPase/BrdU、GFAP/BrdU阳性细胞增多(P<0.05),脑梗死+阿托品组NeuN/Br-dU、CNPase/BrdU阳性细胞减少(P<0.05).结论 胆碱能信号促进NSCs在脑梗死周围区向神经元、少突胶质细胞和星形胶质细胞共同分化,减轻脑水肿,促进脑梗死后神经功能恢复.%Objective To investigate the effects of cholinergic signal on neural stem cell(NSC)differenti-ation in peri-infarction region after ischemic stroke. Methods Mice were randomly assigned into sham + vehicle group,middle cerebral artery occlusion(MCAO)+ vehicle group,MCAO + donepezil group and MCAO + atro-pine group(n = 25). MCAO was induced by thread-occlusion method. Modified neurological severity score (mNSS)was used to evaluate neurological function recovery,and the brain water content was measured by dry-wet weight method. NeuN/5-bromodeoxyuridine(BrdU),CNPase/BrdU,GFAP/BrdU double-labeled cells were tested by immunofluorescence. Results Brain water content of MCAO + vehicle group was significantly higher than that of sham operation group(P < 0.05). Donepezil-treated MCAO mice had lower neurologic deficit scores and brain water content than of MCAO + vehicle group(P < 0.05). On day 14 and day 28 after MCAO,the NeuN/BrdU, CNPase/BrdU and GFAP/BrdU immune-positive cells of MCAO + vehicle group were markedly increased as com-pared with that of sham+vehicle group(P<0.05).Compared with that of MCAO+vehicle group,the number of NeuN/BrdU-positive cells,CNPase/BrdU-positive cells and GFAP/BrdU-positive cells was higher in MCAO+done-pezil group,and the number of NeuN/BrdU-positive cells and CNPase/BrdU-positive cells of MCAO + atropine group was lower(P < 0.05). Conclusions Cholinergic signal could promote NSCs differentiation in peri-infarc-tion region,a lleviate cerebral edema,and improve the brain function restoration after stroke.