Effects of primary microglia and astrocytes on neural stem cells in in vitro and in vivo models of ischemic stroke  

作　　者：Sheng-Jun Wen Xi-Min Zheng Li-Fen Liu Na-Na Li Hai-An Mao Liang Huang Qiong-Lan Yuan 

机构地区：[1]Department of Neurology,Shanghai Tongji Hospital,Tongji University School of Medicine,Shanghai,China

出　　处：《Neural Regeneration Research》2021年第9期1677-1685,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81371213,81070987,30971531;grants from the Ministry of Science and Technology of China,Nos.2010CB945600,2010CB945601(all to QLY)。

摘　　要：Transplantation of neural stem cells(NSCs) can protect neurons in animal stroke models;however, their low rates of survival and neuronal differentiation limit their clinical application. Glial niches, an important location of neural stem cells, regulate survival, proliferation and differentiation of neural stem cells. However, the effects of activated glial cells on neural stem cells remain unclear. In the present study, we explored the effects of activated astrocytes and microglia on neural stem cells in vitro stroke models. We also investigated the effects of combined transplantation of neural stem cells and glial cells after stroke in rats. In a Transwell co-culture system, primary cultured astrocytes, microglia or mixed glial cells were exposed to glutamate or H_2O_2 and then seeded in the upper inserts, while primary neural stem cells were seeded in the lower uncoated wells and cultured for 7 days. Our results showed that microglia were conducive to neurosphere formation and had no effects on apoptosis within neurospheres, while astrocytes and mixed glial cells were conducive to neurosphere differentiation and reduced apoptosis within neurospheres, regardless of their pretreatment. In contrast, microglia and astrocytes induced neuronal differentiation of neural stem cells in differentiation medium, regardless of their pretreatment, with an exception of astrocytes pretreated with H_2O_2. Rat models of ischemic stroke were established by occlusion of the middle cerebral artery. Three days later, 5 × 10~5 neural stem cells with microglia or astrocytes were injected into the right lateral ventricle. Neural stem cell/astrocyte-treated rats displayed better improvement of neurological deficits than neural stem cell only-treated rats at 4 days after cell transplantation. Moreover, neural stem cell/microglia-, and neural stem cell/astrocyte-treated rats showed a significant decrease in ischemic volume compared with neural stem celltreated rats. These findings indicate that microglia and astrocytes exert different e

关 键 词：ASTROCYTES GLUTAMATE MICROGLIA neural stem cells NEUROGENESIS neurons PEROXIDE repair stroke 

分 类 号：R743.3[医药卫生—神经病学与精神病学]