胚胎神经干细胞（hNSC）移植对脑外伤海马神经元轴突损伤的修复及其与CaN-NFAT信号通路的关系

Human neural stem cell(hNSC) transplantation is useful to faciliate recovery of learning and memory in rats suffering from traumatic brain injury(TBI). However, the underlying mechanisms remains elusive. Our previous study has suggested that human NSC (hNSC) via releasing glial cell line-derived neurotrophic factor (GDNF), promoted cognitive function in rats following traumatic brain injury, and the expression of amyloid precursor protein swelling (App swelling, the marker of damaged axon) in TBI+hNSC groups is lower than its expression in TBI groups. Hence, we assume that hNSC grafts maybe facilitate the recovery of traumatic axonal injury. Because calcineurin (CaN) is the drownstream signal factor of GDNF and CaN-NFAT signaling pathway is also responsible for the recovery of traumatic axonal injury, we also assume that hNSC promoting cognitive function in rats following TBI has relationship with CaN-NFAT signal pathway. Based on our previous study, this project is to further test the recovery of traumatic axonal injury after hNSC transplantation and the activity of CaN. then, we inhibit the activity of CaN and test the recovery of damaged axon and NFAT expression. In all, this project can identify the molecular mechanism of hNSC transplantation and provide theoretical support of hNSC graft in the treatment of traumatic brain injury.

胚胎神经干细胞（hNSC）移植可以提高脑外伤（TBI）动物的学习和记忆功能，但具体的作用机制仍然不清。本课题前期研究发现，移植入动物脑内的hNSC可以分泌胶质细胞源性生长因子（GDNF）从而促进脑外伤神经功能的恢复，而且hNSC组较对照组，动物海马区神经元App“收缩球”（轴突损伤标志）的表达明显减少，因而推测hNSC可能通过促进海马神经元轴突损伤的修复，来发挥神经保护作用；由于钙神经酶（CaN）为GDNF下游的信号分子，且CaN-NFAT信号通路与轴突的损伤修复密切相关，因此推测hNSC促进轴突的损伤修复可能与CaN-NFAT信号通路有关。本课题拟在前期研究基础上，进一步验证hNSC对海马神经元轴突的损伤修复，并观察CaN的活性变化；进而抑制CaN活性，观察轴突损伤的修复及NFAT表达的变化。本研究旨在明确hNSC促进脑外伤神经功能恢复的作用机制，为hNSC治疗脑外伤提供理论支持。

胚胎神经干细胞移植可以修复脑外伤大鼠的学习和记忆功能，但是具体的机制仍需研究，通过本研究我们发现：一是胚胎神经干细胞(hNSC)移植对脑外伤海马神经元轴突损伤有修复关系；二是这种修复关系与CaN-NFAT信号通路有关。本研究的意义在于明确了胚胎神经干细胞(hNSC)移植治疗脑外伤的作用机制，为hNSC移植治疗脑外伤提供理论依据。