AUTHOR=Edwards Katie A. , Pattinson Cassandra L. , Guedes Vivian A. , Peyer Jordan , Moore Candace , Davis Tara , Devoto Christina , Turtzo L. Christine , Latour Lawrence , Gill Jessica M. 

TITLE=Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00348

DOI=10.3389/fneur.2020.00348

ISSN=1664-2295

ABSTRACT=<p><bold>Introduction:</bold> Elevated levels of blood-based proinflammatory cytokines are linked to acute moderate to severe traumatic brain injuries (TBIs), yet less is known in acute mild (m)TBI cohorts. The current study examined whether blood-based cytokines can differentiate patients with mTBI, with and without neuroimaging findings (CT and MRI).</p><p><bold>Material and Methods:</bold> Within 24 h of a mTBI, determined by a Glasgow Coma Scale (GCS) between 13 and 15, participants (<italic>n</italic> = 250) underwent a computed tomography (CT) and magnetic resonance imaging (MRI) scan and provided a blood sample. Participants were classified into three groups according to imaging findings; (1) CT+, (2) MRI+ (CT–), (3) Controls (CT– MRI–). Plasma levels of circulating cytokines (IL-6, IL-10, TNFα), and vascular endothelial growth factor (VEGF) were measured using an ultra-sensitive immunoassay.</p><p><bold>Results:</bold> Concentrations of inflammatory cytokines (IL-6, TNFα) and VEGF were elevated in CT+, as well as MRI+ groups (<italic>p</italic> &lt; 0.001), compared to controls, even after controlling for age, sex and cardiovascular disease (CVD)-related risk factors; hypertension, and hyperlipidemia. Post-concussive symptoms were associated with imaging groupings, but not inflammatory cytokines in this cohort. Levels of VEGF, IL-6, and TNFα differentiated patients with CT+ findings from controls, with the combined biomarker model (VEGF, IL-6, TNFα, and IL-10) showing good discriminatory power (AUC 0.92, 95% CI 0.87–0.97). IL-6 was a fair predictor of MRI+ findings compared to controls (AUC 0.70, 95% CI 0.60–0.78). Finally, the combined biomarker model discriminated patients with MRI+ from CT+ with an AUC of 0.71 (95% CI 0.62–0.80).</p><p><bold>Conclusions:</bold> When combined, IL-6, TNFα, and VEGF may provide a promising biomarker cytokine panel to differentiate mTBI patients with CT+ imaging vs. controls. Singularly, IL-6 was a fair discriminator between each of the imaging groups. Future research directions may help elucidate mechanisms related to injury severity and potentially, recovery following an mTBI.</p>