神经干细胞和嗅鞘细胞联合移植促进创伤性脑外伤大鼠神经功能修复的分子机制研究

The molecular mechanism of traumatic brain injury (TBI) repair and treatment is the focus of the basic medical research. Cell transplantation plays an important role in the therapy of nervous system diseases such as spinal cord injury and brain injury, but the underlying molecular mechanism is unclear now. This study is based on the preliminary study entitled “Co-grafting of neural stem cells with olfactory ensheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism”. However, we hypothesize that except anti-inflammatory and anti-apoptosis mechanism, co-grafting may enhance the synaptic connection between endogenous and exogenous neurons, promote  the neurite  outgrowth and secrete many neurotrophic factors for the injury sites microenvironment improvement to treat TBI. And we will use the neuroethology, morphology, in vivo and vitro experiment to explore the effect of co-grafting on synaptic activity, axon growth and neurotrophic factors expression; and also inject the drug which increases NSCs differentiation into neurons or the drug which removes neurons function to explore the role of neurons in neuronal repair. We aim to more completely elucidate its underlying molecular mechanisms.

创伤性脑外伤（TBI）修复和治疗的分子机制是基础医学研究焦点。细胞移植在治疗神经系统疾病如脊髓损伤和脑外伤中发挥重要作用，但其分子机制尚不清楚。本项目是前期研究“神经干细胞（NSCs）和嗅鞘细胞（OECs）联合移植通过抗炎反应促 TBI 大鼠神经功能修复”的深入和延续。本课题提出除了抗炎抗凋亡反应以外，联合移植也可能通过增加内源和外源神经元之间的突触联系，促进轴突再生和分泌多种神经营养因子改善损伤区微环境而治疗和改善 TBI 的假说。课题将通过神经行为学、形态学、体内和体外实验观察联合移植对突触活动、轴突生长及损伤区多种神经营养因子表达的影响；通过体内注射促 NSCs 靶向分化为神经元药物或注射去除神经元功能的药物观察神经元在神经修复中是否具有关键作用。以期更全面的揭示 NSCs 和 OECs 联合移植改善 TBI 的分子生物学机制。

创伤性脑外伤（TBI）修复和治疗的分子机制是基础医学研究焦点。细胞移植在治疗神经系统疾病如脊髓损伤和脑外伤中发挥重要作用，但其分子机制尚不清楚。本项目是前期研究“神经干细胞（NSCs）和嗅鞘细胞（OECs）联合移植通过抗炎反应促 TBI 大鼠神经功能修复”的深入和延续。本课题提出除了抗炎抗凋亡反应以外，联合移植也可能通过增加内源和外源神经元之间的突触联系，促进轴突再生和分泌多种神经营养因子改善损伤区微环境而治疗和改善 TBI 的假说。课题将通过神经行为学、形态学、体内和体外实验观察联合移植对突触活动、轴突生长及损伤区多种神经营养因子表达的影响；通过体内注射促 NSCs 靶向分化为神经元药物或注射去除神经元功能的药物观察神经元在神经修复中是否具有关键作用。以期更全面的揭示 NSCs 和 OECs 联合移植改善 TBI 的分子生物学机制。