Abstract
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.
Authors
Jiaqi Jin, Fang Wang, Jiawei Tian, Xinyi Zhao, Jiawei Dong, Nan Wang, Zhihui Liu, Hongtao Zhao, Wenqiang Li, Ge Mang, Shaoshan Hu
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