Differences in the neuronal stem cells survival, neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury
Differences in the neuronal stem cells survival, neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury
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DOI：
10.2152/jmi.53.42
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发表时间：
2006-02-01
影响因子：
0.7
通讯作者：
Nagao, Seigo
中科院分区：
文献类型：
--
作者：
Shindo, Tokuhisa;Matsumoto, Yoshihito;Nagao, Seigo
我们开发了一种新的方案，用于从小鼠胚胎干细胞（ESC）中生成和选择性扩增区域特异于嘴脑而非脊髓的神经祖细胞。神经祖细胞可以在体外和体内分化为许多胆碱能神经元和一些GABA能神经元，但很少分化为星形胶质细胞。移植的神经球可以在患有轻度创伤性脑损伤（TBI）的动物的海马体（CA3）中存活。移植后十二周（行为测试后一周），我们发现 eGFP+ 移植细胞中存在显着的胆碱能分化，被识别为 ChAT 免疫反应性。此外，移植物含有一些 GAD67+ 细胞。然而，我们在移植物中几乎没有发现 GFAP+ 星形胶质细胞。此外，移植物来源的神经元的突触前形成通过 CA3 周围移植物附近的免疫组织化学识别。然而，在严重 TBI 组中并未观察到这些结果。因此，我们通过RT-PCR检测了12只小鼠（包括正常组、轻度TBI组和重度TBI组）的NGF、BDNF和FGF-2 mRNA。轻度TBI组同侧海马神经营养因子mRNA明显增加。统计分析显示轻度和重度 TBI 组之间存在显着差异。数据还显示轻度 TBI 组和正常组之间存在显着差异。移植的神经球可以在轻度 TBI 动物中存活，但在严重 TBI 组中则不能。
We developed a novel protocol for generation and selective amplification of neural progenitor cells regionally specified to the rostral brain but not the spinal cord from mouse embryonic stem cells (ESCs). The neural progenitors could differentiate in vitro and in vivo in to many cholinergic and a few GABA ergic neurons but rarely into astrocytes. The transplanted neurospheres could survive in the hippocampus (CA3) of animals with mild traumatic brain injury (TBI). Twelve weeks after transplantation (a week after the behavioral test), we found significant cholinergic differentiation recognized as ChAT immunoreactivity in the eGFP+ transplanted cells. Moreover, the grafts contained a few GAD67+ cells. However, we barely found GFAP+ astrocytes within the grafts. Furthermore, presynaptic formations of graft-derived neurons were recognized by immunohistochemistry of near the grafts around CA3. However, these findings were not observed in severe TBI group. So, we examined NGF, BDNF, and FGF-2 mRNA by RT-PCR in 12 mice including normal, mild TBI and severe TBI group. Increases in the neurotrophic factors' mRNA were evident in the hippocampus on the ipsilateral side in the mild TBI group. Statistical analysis revealed significant differences between the mild and severe TBI groups. The data also revealed significant differences between the mild TBI and normal groups. The transplanted neurospheres could survive in the mild TBI animals, but not in the severe TBI group.