He Zhenghui, Lang Lijian, Hui Jiyuan, Ma Yuxiao, Yang Chun, Weng Weiji, Huang Jialin, Zhao Xiongfei, Zhang Xiaoqi, Liang Qian, Jiang Jiyao, Feng Junfeng
Brain Injury Center, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
J Clin Med. 2022 May 11;11(10):2709. doi: 10.3390/jcm11102709.
After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplantation.
Brain extracts of TBI mice were used in vitro to simulate the different phase TBI influences on the differentiation of human NSCs. Protein profiles of brain extracts were analyzed. Neuronal differentiation and the activation of autophagy and the WNT/CTNNB pathway were detected after brain extract treatment.
Under subacute TBI brain extract conditions, the neuronal differentiation of hNSCs was significantly higher than that under acute brain extract conditions. The autophagy flux and WNT/CTNNB pathway were activated more highly within the subacute brain extract than in the acute brain extract. Autophagy activation by rapamycin could rescue the neuronal differentiation of hNSCs within acute TBI brain extract.
The subacute phase around 7 days after TBI in mice could be a candidate timepoint to encourage more neuronal differentiation after transplantation. The autophagy flux played a critical role in regulating neuronal differentiation of hNSCs and could serve as a potential target to improve the efficacy of transplantation in the early phase.
创伤性脑损伤（TBI）后，细胞环境发生显著变化，这对移植的神经干细胞（NSCs）产生多种影响。目前，这些对神经干细胞的影响尚未完全阐明，这阻碍了寻找神经干细胞移植的最佳时间点。
使用TBI小鼠的脑提取物在体外模拟TBI不同阶段对人神经干细胞分化的影响。分析脑提取物的蛋白质谱。在脑提取物处理后检测神经元分化以及自噬和WNT/CTNNB途径的激活情况。
在亚急性TBI脑提取物条件下，人神经干细胞的神经元分化明显高于急性脑提取物条件下的。亚急性脑提取物中的自噬通量和WNT/CTNNB途径的激活程度高于急性脑提取物。雷帕霉素激活自噬可挽救急性TBI脑提取物中hNSCs的神经元分化。
小鼠TBI后约7天的亚急性期可能是促进移植后更多神经元分化的候选时间点。自噬通量在调节hNSCs的神经元分化中起关键作用，可作为提高早期移植疗效的潜在靶点。
