利用光遗传技术提高神经干细胞存活及分化率促进脑缺血康复的实验研究

实验提示神经干细胞移植可促进脑缺血后的神经功能康复，但外源性干细胞移植后的存活和分化能力十分有限,提高移植干细胞的存活和分化能力对提高神经干细胞的疗效至关重要。目前研究发现光遗传技术可通过调控电活动，影响神经干细胞的增殖。我们前期研究提示利用光遗传学抑制纹状体神经元活性可以促进神经干细胞的分化并减轻缺血性脑损伤。因此，我们拟进一步利用光遗传技术，在大脑中动脉缺血模型中探索通过光遗传技术调控电活动是否能促进移植后神经干细胞的存活和分化，从而提高疗效。本项目将研究：1）光遗传调控移植神经干细胞的电活动是否能促进脑缺血后的神经功能改善；2）调控移植神经干细胞的电活动对其存活和分化的影响；3）光遗传调控移植神经干细胞电活动影响其存活和分化的机制。本研究的结果将有助于明确光调控神经干细胞电活动治疗脑缺血的作用及其机制，为脑缺血以及其它神经系统疾病治疗提供提供一个全新的思路。

Experimental data indicated that neural stem cells (NSCs) transplantation improved neuronal function recovery after ischemic stroke. Because of low survival rate and differentiation ability, it is crucial to promote survival and differentiation of NSCs grafts to improve the efficiency of NSCs based therapy in cerebral ischemia. Previous studies demonstrated that optogenetics tools could regulate electrical activity and influence the proliferation of NSCs. Our previous data suggested that optogenetics inhibition of striatum neuron promoted differentiation of NSCs and attenuated ischemic injuries.However, it is unclear that whether regulation the electrical activity of exogenous NSCs via optogentics tool could increase the surviaval and differentiation and improve efficiency of NSCs treatment? In this study, optogentics tool will be applied to regulate the activity of transplanted NSCs in middle cerebral artery occlusion (MCAO) model to investigate: 1) whether regulation the electrical activity of transplanted NSCs via optogenetics tools could improve efficiency of NSCs treatment , 2) the effect of electrical activity on the survival and differentiation of transplanted NSCs , 3) the mechanisn of electrical activity on the survival and differentiation of transplanted NSCs. The results of this study will extend the mechanisms of neural stem cells in the treatment of cerebral ischemia and provide solid evidence and valid method in the treatment of cerebral ischemia as well as other centre nervous system diseases.