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人源胚胎神经干细胞移植可对抗大鼠的脑缺血/再灌注损伤

刘晓燕, 王昌鹏, 刘铭, 季刚, 郭景春^*

复旦大学上海医学院神经生物系，医学神经生物学国家重点实验室，上海 200032

摘要

本文旨在研究人源胚胎神经干细胞(human embryonic neural stem cells, hNSCs)移植到脑缺血/再灌注损伤大鼠脑内后的迁移、分化，以及对大鼠脑卒中的疗效。我们在大脑中动脉栓塞(middle cerebral artery occlusion, MCAO) 1 h的大鼠模型上，于血流再灌注后第7天注射hNSCs到缺血侧侧脑室，通过焦油紫染色测量大鼠的脑梗死体积，通过检测大鼠的感觉运动行为评估其神经功能的恢复水平，通过免疫荧光共标观察移植后的hNSCs在脑内的迁移与分化。结果显示，hNSCs移植后能够显著减小脑卒中大鼠脑梗死体积，并改善脑卒中大鼠的转棒、错步和转角等运动行为能力；侧脑室注射的hNSCs优先向胼胝体以及梗死区周边迁移，迁移到胼胝体的hNSCs可以分化成少突胶质细胞和星形胶质细胞，迁移到梗死区周边的细胞能够分化成神经元。以上这些结果提示，侧脑室移植的hNSCs可能通过向特定脑区的迁移和分化发挥对脑缺血/再灌注损伤大鼠的保护作用。

关键词： 脑卒中; 神经干细胞; 少突胶质细胞再生

分类号：Q189

[Transplantation of human embryonic neural stem cells protects rats against cerebral ischemic injury.] [Article in Chinese]

LIU Xiao-Yan, WANG Chang-Peng, LIU Ming, JI Gang, GUO Jing-Chun^*

State Key Laboratory of Medical Neurobiology, Department of Neurobiology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract

The purpose of this study is to explore the fate and effect of human embryonic neural stem cells (hNSCs) after transplantation into ipsilateral lateral ventricle of stroke rats. Adult rats were exposed to one-hour transient middle cerebral artery occlusion (MCAO), and then hNSCs were transplanted into ipsilateral lateral ventricle 7 days after reperfusion. Infarct volume was calculated by cresyl violet staining. The improvements of neural functions were assessed by behavioral tests. Immunofluorescence staining was performed to observe the migration and differentiation of transplanted hNSCs. The results showed that transplanted hNSCs significantly reduced ischemia-induced infarction in MCAO rats, and improved neural functional restoration when assessed by rotarod, footfault and corner-turn tests. The grafted cells migrated predominantly to several specific brain regions, such as corpus callosum and peri-infarct area. Furthermore, these cells differentiated into oligodendrocytes and astrocytes in corpus callosum, and neurons in peri-infarct parenchyma. These results suggest that transplanted hNSCs through lateral ventricle of the ischemic side may exert effective therapeutic effects on stroke rats via migration and differentiation in specific brain regions.

Key words: stroke; neural stem cell; oligodendrogenesis

收稿日期：2014-09-26　　录用日期：2014-10-30

通讯作者：郭景春　　E-mail: jingchunguo@shmu.edu.cn

引用本文：

刘晓燕, 王昌鹏, 刘铭, 季刚, 郭景春. 人源胚胎神经干细胞移植可对抗大鼠的脑缺血/再灌注损伤[J]. 生理学报 2014; 66 (6): 691-701.

LIU Xiao-Yan, WANG Chang-Peng, LIU Ming, JI Gang, GUO Jing-Chun. [Transplantation of human embryonic neural stem cells protects rats against cerebral ischemic injury.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (6): 691-701 (in Chinese with English abstract).