Serum neutrophil extracellular trap-related biomarkers for identifying cognitive impairment after mild traumatic brain injury.

BACKGROUND: Cognitive impairment is a common sequela of mild traumatic brain injury (mTBI), but early blood-based predictors remain limited. Neutrophil extracellular traps (NETs) have been implicated in neuroinflammation after brain injury. AIMS: We investigated whether serum NET-related markers are associated with mild cognitive impairment (MCI) after mTBI and evaluated their utility for early risk stratification. METHODS: A total of 157 patients with acute mTBI and 88 age- and sex-matched healthy controls (HCs) were enrolled in this retrospective cohort study. Blood samples were collected within 72 h after injury, and cognitive status was assessed at the 3-month follow-up. The patients were classified as mTBI without MCI (n = 80) or mTBI with MCI (n = 77). Peripheral blood cell and serum NET-related markers were measured. Multivariable logistic regression was used to identify factors independently associated with post-mTBI MCI, and receiver operating characteristic (ROC) analysis was performed to assess discrimination. RESULTS: Compared with HCs, patients with mTBI showed significant alterations in white blood cells, hemoglobin, platelets, neutrophil count (NEUT), lymphocytes, and eosinophils. Compared with patients without MCI, those with MCI had significantly higher levels of white blood cell count, NEUT, IL-8, IL-1β, IL-17A, IFN-α, dsDNA, myeloperoxidase (MPO), and citrullinated histone H3, but lower levels of TNF-α and vascular endothelial growth factor (VEGF). In multivariable analysis, NEUT, MPO, dsDNA, and IL-8 were independently associated with post-mTBI MCI. The combined biomarker model showed good discrimination (AUC = 0.896). DISCUSSION: Serum NET-related markers are associated with cognitive impairment after mTBI. A biomarker panel incorporating NEUT, MPO, dsDNA and IL-8 may help identify patients at increased risk of post-mTBI MCI.