Faculty Collaboration Database

Inflammatory blood-based biomarkers to aid in the assessment and prognostication of traumatic brain injury: a TRACK-TBI study. J Neuroinflammation 2026 May 28;23(1)

Date

05/29/2026

Pubmed ID

42210282

Pubmed Central ID

PMC13430862

DOI

10.1186/s12974-026-03891-3

Scopus ID

2-s2.0-105046513624 (requires institutional sign-in at Scopus site)

Abstract

BACKGROUND: Inflammatory proteins detectable in blood reflect pathoanatomic injury patterns after traumatic brain injury (TBI). Identifying biomarkers of secondary neurologic and systemic injury may improve detection of patients at risk for clinical decline and chronic disability. This study examined the utility of acute and subacute inflammatory biomarkers to differentiate TBI diagnosis and severity, and predict 6-month outcomes.

METHODS: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study prospectively enrolled TBI patients presenting to 18 United States trauma centers with head computed tomography (CT) on day 1 (D1; < 24-h post-injury). Data were extracted from TRACK-TBI subjects with D1 and 2-week (W2) plasma samples and 6-month functional outcomes, yielding 369 TBI subjects, 100 orthopedic trauma controls (OC), and 69 healthy controls. Twenty-seven inflammatory biomarkers were analyzed (MesoScale Diagnostics). TBI severity was defined using Glasgow Coma Scale (GCS; 3-12/13-15) and radiographic intracranial injury (CT-positive/CT-negative). Multivariable logistic regressions examined biomarkers as predictors of 6-month unfavorable outcomes (Glasgow Outcome Scale-Extended = 1-4 (death/severe-disability)), and adjusted for clinico-demographic factors and multiple comparisons. Adjusted odds ratios (AOR [95% confidence interval]) per log₂-unit increase in biomarker level were reported.

RESULTS: Ten biomarkers (c-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-1ꞵ, IL-2, IL-4, IL-6, IL-10, IL-15, IL-17A, tumor necrosis factor (TNF)-α) differed significantly between GCS 3-12 vs. 13-15 TBI, CT-positive vs. CT-negative TBI, and GCS 3-12 TBI vs. OC, at both D1 and W2 (p < 0.001). IL-6, CRP, and SAA showed good discrimination of clinical TBI severity (D1/W2 area under-the-curve (AUC): 0.87/0.87, 0.82/0.88, 0.80/0.85, respectively), and moderate-to-good discrimination of radiographic TBI severity (D1/W2 AUC: 0.81/0.82, 0.78/0.83, 0.77/0.79, respectively). Five W2 biomarkers emerged as multivariable predictors of 6-month unfavorable outcomes (IL-15: AOR = 2.26 [1.14-4.49]; SAA: AOR = 1.91 [1.37-2.67]; IL-6: AOR = 1.80 [1.25-2.61]; IL-17A: AOR = 1.72 [1.24-2.39]; CRP: AOR = 1.40 [1.06-1.85]).

CONCLUSIONS: Ten circulating inflammatory proteins were associated with TBI diagnosis and severity at D1 and W2. Of these, five biomarkers expressed subacute (W2) levels predictive of 6-month death/severe-disability, underscoring their potential for validation as a novel biomarker class and integration into TBI prognostic models. Distillation of pro- and anti-inflammatory biomarker cascades in TBI could facilitate precision medicine approaches for risk stratification and therapeutic modulation.

Author List

Yue JK, Fu AY, Jain S, Puccio AM, Eagle SR, Korley FK, van Essen TA, Samanta R, Li LM, Roberts CJ, Caldwell DJ, Elguindy MM, Vassar MJ, Belton PJ, Bhattacharyay S, Nelson LD, Tracey JX, Etemad LL, Gotthardt CJ, Satris GG, Wang MB, Demos C, Sigal GB, Amorim E, Madhok DY, Radabaugh HL, Ferguson AR, Markowitz AJ, Robertson CS, Valadka AB, Mukherjee P, Yuh EL, McCrea MA, Hinson HE, Schneider ALC, Sun X, Okonkwo DO, Kobeissy FH, Manley GT, Diaz-Arrastia R, Wang KKW, TRACK-TBI Investigators

Authors

Michael McCrea PhD Interim Senior Associate Dean, Professor in the Neurosurgery department at Medical College of Wisconsin
Lindsay D. Nelson PhD Professor in the Neurosurgery department at Medical College of Wisconsin
Christopher J. Roberts PhD, MD Associate Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Biomarkers
Brain Injuries, Traumatic
Cytokines
Female
Glasgow Coma Scale
Humans
Inflammation
Male
Middle Aged
Prognosis
Prospective Studies
Young Adult