颅脑损伤（TBI）后交感兴奋与患者预后密切相关，课题组研究发现下丘脑室旁核（PVN）氧化应激是TBI后交感兴奋的重要病理基础，但机制尚不清楚。进一步临床研究发现，中性粒细胞胞外陷阱（NETs）与TBI后交感兴奋有关。而氧化应激是NETs形成（NETosis）的经典途径。NETs中LL37可促进小胶质细胞分泌IL-1β；IL-1β是多种病理情况下交感兴奋的重要原因。同时，课题组通过大鼠PVN组织蛋白芯片检测发现KLF9/NDUFS1在TBI后表达发生变化，可能通过调控氧化应激参与NETs形成。因此，我们假设TBI后，PVN内KLF9/NDUFS1通过氧化应激调控NETs形成，进而通过Hippo通路促进小胶质细胞分泌IL-1β，最终影响交感兴奋。本课题拟利用大鼠弥漫性轴索损伤模型，在临床、细胞、分子和动物水平研究TBI后NETosis机制及NETs影响交感兴奋的机制，以期为临床治疗提供新靶点。

Sympathetic hyperactivity is closely associated with the prognosis of patients with traumatic brain injury (TBI). We have previously found that oxidative stress in paraventricular nucleus (PVN) of hypothalamus plays an important part in sympathetic hyperactivity after TBI, but the mechanism is unclear. We have also detected that neutrophil extracellular traps (NETs) are associated with sympathetic hyperactivity after TBI in clinical studies, while oxidative stress is the classical way in the formation of NETs (NETosis). LL37 in NETs can promote the secretion of IL-1β by microglia, which contributes to sympathetic hyperactivity under various pathological conditions. Meanwhile, we found that the abnormal expression of KLF9/NDUFS1 signaling axis after TBI may participate in the formation of NETs through regulating oxidative stress. Therefore, we hypothesize that KLF9/NDUFS1 in PVN regulate NETs formation through oxidative stress after TBI. NETs then activate the secretion of IL-1β by microglia via Hippo pathway, ultimately leading to sympathetic hyperactivity. This study is designed to explore the mechanism of NETosis after TBI and the influence of NETs on sympathetic hyperactivity at clinical, cellular, molecular and animal levels using rat diffuse axonal injury model. We intend to provide a new target for the clinical treatment of sympathetic hyperactivity after TBI.