Coagulopathy contributes to the majority of deaths and disabilities associated with traumatic brain injury (TBI). Whether neutrophil extracellular traps (NETs) contribute to an abnormal coagulation state in the acute phase of TBI remains unknown. Our objectives were to demonstrate the definitive role of NETs in coagulopathy in TBI. We detected NET markers in 128 TBI patients and 34 healthy individuals. Neutrophil-platelet aggregates were detected in blood samples from TBI patients and healthy individuals using flow cytometry and staining for CD41 and CD66b. Endothelial cells were incubated with isolated NETs and we detected the expression of vascular endothelial cadherin, syndecan-1, thrombomodulin, von Willebrand factor, phosphatidylserine, and tissue factor. In addition, we established a TBI mouse model to determine the potential role of NETs in TBI-associated coagulopathy. NET generation was mediated by high mobility group box 1 (HMGB1) from activated platelets and contributed to procoagulant activity in TBI. Furthermore, coculture experiments indicated that NETs damaged the endothelial barrier and caused these cells to assume a procoagulant phenotype. Moreover, the administration of DNase I before or after brain trauma markedly reduced coagulopathy and improved the survival and clinical outcome of mice with TBI.

中文翻译：

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中性粒细胞胞外陷阱导致创伤性脑损伤后的凝血病

大多数与创伤性脑损伤 (TBI) 相关的死亡和残疾都与凝血病有关。中性粒细胞胞外陷阱 (NETs) 是否会导致 TBI 急性期异常凝血状态仍然未知。我们的目标是证明 NETs 在 TBI 凝血病中的决定性作用。我们在 128 名 TBI 患者和 34 名健康人中检测到了 NET 标记。使用流式细胞术和 CD41 和 CD66b 染色在 TBI 患者和健康个体的血液样本中检测到中性粒细胞-血小板聚集体。内皮细胞与分离的 NETs 一起孵育，我们检测了血管内皮钙粘蛋白、syndecan-1、血栓调节蛋白、von Willebrand 因子、磷脂酰丝氨酸和组织因子的表达。此外，我们建立了 TBI 小鼠模型来确定 NET 在 TBI 相关凝血病中的潜在作用。NET 的生成由来自活化血小板的高迁移率族框 1 (HMGB1) 介导，并有助于 TBI 中的促凝血活性。此外，共培养实验表明 NETs 破坏了内皮屏障并导致这些细胞呈现促凝血表型。此外，在脑外伤之前或之后施用 DNase I 可显着减少凝血病并改善 TBI 小鼠的存活率和临床结果。共培养实验表明 NETs 破坏了内皮屏障并导致这些细胞呈现促凝血表型。此外，在脑外伤之前或之后施用 DNase I 可显着减少凝血病并改善 TBI 小鼠的存活率和临床结果。共培养实验表明 NETs 破坏了内皮屏障并导致这些细胞呈现促凝血表型。此外，在脑外伤之前或之后施用 DNase I 可显着减少凝血病并改善 TBI 小鼠的存活率和临床结果。