颅脑创伤（TBI）具有高发生率、死亡率和致残率的突出特点，但目前尚缺乏安全有效的治疗措施。TrkB信号通路参与TBI病生与神经功能恢复过程。N-乙酰5-羟色胺（NAS）为TrkB受体激动剂，具有抗氧化与抗凋亡等特性，然而NAS对TBI的作用机制尚不清楚。基于申请人前期工作基础，推测TBI后NAS通过TrkB/PI3K/Akt/Nrf2通路介导氧化应激与铁死亡改善神经功能。本项目拟利用TrkB-/-小鼠建立TBI模型，采用siRNA细胞转染与共培养等开展：①阐明NAS通过TrkB受体改善TBI后脑损害与神经功能的作用机制；②揭示TBI后NAS依赖于TrkB经典下游分子介导氧化应激与铁死亡发挥功能的信号机制；③探讨以上分子机制间的调控关系及NAS参与星型胶质细胞保护神经元的分子机理。通过上述研究，为揭示TBI后NAS的脑保护作用机制提供理论依据，有望为TBI治疗与预后判断提供新的策略和思路。

The occurrence of traumatic brain injury (TBI) has the characteristics of high incidence, mortality and morbidity. Recently, there is no safe and effective treatment. Tyrosine receptor kinase B (TrkB) signal pathway is involved in pathophysiology and neurological function repair after TBI. N-acetyl-serotonin (NAS), an agonist of the TrkB receptor, exerts the effects of anti-oxidative stress and anti-apoptosis. Yet, its possible effects on TBI remain poorly understood. Based on the applicant's previous research work on TBI, we speculate that NAS attenuates TBI-induced oxidative stress and ferroptosis by acting on TrkB/PI3K/Akt/Nrf2 signal pathway, and also restores neurological function. Using TrkB gene knockout mice to receive an experimental TBI model, by utilizing siRNA transfection and co-culture techniques, the project is designed to carry out the studies in vivo and in vitro as follows: ① To clarity the effects of NAS on brain damage, and neurological function by acting on TrkB receptors after TBI ; ② To explore the signal mechanisms underlying the neuroprotective effect of NAS by acting on the downstream signaling pathways of TrkB including oxidative stress and gerroptosis; ③ To further explore the regulatory relationship of the above signal pathways, and the molecular mechanisms underlying NAS involved in the process of astrocytes-protecting neurons. Based on the above studies, this proposal is expected to provide a new theoretical basis for the protective effect of NAS on brain after TBI, and to provide new strategies and ideas for the treatment and prognosis of TBI patients.