创伤性脑损伤(TBI)致残、致死率高。文献和申请人既往研究证实：NSCs具有修复脑损伤的作用，TBI后再生微环境中TLR4介导的小胶质细胞M1型活化影响NSCs再生能力，但调控机制不明。我们前期研究发现：TBI后NSCs产生的外泌体可抑制小胶质细胞M1表型，NSCs外泌体lncRNA表达谱分析：TUNA变化最为显著。生物信息学分析：TLR4通路有TUNA的作用位点。提示：TBI后NSCs外泌体lncRNA-TUNA通过TLR4信号调控小胶质细胞的表型与功能，影响NSCs的再生微环境。本课题研究TBI后再生微环境中NSCs外泌体lncRNA-TUNA的表达变化特征；明确其作用于小胶质细胞TLR4通路的位点与方式；揭示其改变小胶质细胞表型调控NSCs再生的作用机制与效应；建立NSCs外泌体目标干预策略，促进神经再生修复。本研究有望发现调控再生微环境炎症反应新分子，也将是中枢再生研究的新突破。

Traumatic brain injury (TBI) is a kind of disease with high disability and lethality. The literature and our previous research demonstrated that neural stem cells (NSCs) had the ability to repair the injured brain, and the TLR4 mediated M1 phenotype activation of microglia could influence the neurogenesis ability of NSCs after TBI, but the involved mechanisms were not clear. We had found that NSCs derived exosomes could inhibit the M1 polarization of microglia after TBI, and the lncRNA-TUNA was the most obvious changed one in the exosomal lncRNA expression profile analysis. The bioinformatics analysis indicated that lncRNA-TUNA could target TLR4 pathway. All the above results indicated that NSCs derived exosomal lncRNA-TUNA has the potential to influence the neurogenic niche through modulating the phenotype and function of microglia by targeting TLR4 pathway after TBI. The objective of this research is to analysis the expression feature of NSCs derived exosomal lncRNA-TUNA in the neurogenic niche after TBI, clarify the site and approach of NSCs derived exosomal lncRNA-TUNA affecting TLR4 pathway in microglia, uncover the effect and mechanism of exosomal lncRNA-TUNA influencing microglia, and establish NSCs derived exosome intervention strategy to promote neurogenesis. The outcome of this research might be hopeful to discover new molecular that could modulate the neuroinflammation in neurogenic niche, and will be a breakthrough in the neurogenesis research.