LAUSR

Traumatic brain injury (TBI) is characterized by heterogeneity in terms of injury severity, mechanism, outcome, and pathophysiology. A single biomarker alone is unlikely to capture the heterogeneity of even one injury subtype, necessitating the use of panels of biomarkers. Herein, we focus on traumatic cerebrovascular injury and investigate associations of a panel of 16 vascular injury-related biomarkers with indices of TBI severity and outcomes using data from 159 participants in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot Study. Associations of individual biomarkers and clusters of biomarkers identified using non-linear principal components analysis with TBI severity and outcomes were assessed using logistic regression models and Spearman's correlations. As individual biomarkers, higher levels of thrombomodulin, Ang-2, vWF, and P-Selectin were associated with more severe injury; higher levels of Ang-1, Tie2, VEGF-C, and bFGF were associated with less severe injury (all p<0.05 in age-adjusted models). After false discovery rate correction for multiple comparisons, higher levels of Ang-2 remained associated with more severe injury and higher levels of Ang-1, Tie2, and bFGF remained associated with less severe injury at a p<0.05 level. In principal components analysis, PC1 (comprised of Ang1, bFGF, P-selectin, VEGF-C, VEGF-A, and Tie2) was associated with less severe injury (age-adjusted OR: 0.63, 95% CI: 0.44-0.88 for head CT positive versus negative) and PC2 (Ang-2, E-Selectin, Flt-1, PIGF, thrombomodulin, and VCAM-1) was associated with greater injury severity (age-adjusted OR: 2.29, 95% CI: 1.49-3.69 for Glasgow Coma Scale [GCS] 3-12 versus 13-15 and age-adjusted OR 1.59, 95% CI: 1.11-2.32 for head CT positive versus negative). Neither individual biomarkers nor PCs were associated with outcomes in adjusted models (all p>0.05). In conclusion, in this trauma-center based population of acute TBI patients, biomarkers of microvascular injury were associated with TBI severity.