Neutrophil extracellular traps contribute to coagulopathy after traumatic brain injury.

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 process 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 subjects. Neutrophil-platelet (PLT) aggregates were detected in blood samples from TBI patients and healthy subjects using flow cytometry and staining with CD41 and CD66b. Endothelial cells (ECs) were incubated with isolate NETs and detected the expression of vascular endothelial (VE)-cadherin, syncanden-1, thrombomodulin, von Willebrand factor (VWF), phosphatidylserine (PS) and and tissue factor (TF). In addition, we established a TBI mouse model to detect the potential role of NETs in TBI associated coagulopathy. NETs generation was mediated by High Mobility Group Box 1(HMGB1) from activated platelets and contribute 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.