Blood Biomarkers in Moderate-To-Severe Traumatic Brain Injury: Potential Utility of a Multi-Marker Approach in Characterizing Outcome

Abstract

BackgroundBlood biomarkers are valuable tools for elucidating complex cellular and molecular mechanisms underlying traumatic brain injury (TBI). Profiling distinct classes of biomarkers could aid in the identification and characterization of initial injury and secondary pathological processes. This study characterized the prognostic performance of a recently developed multi-marker panel of circulating biomarkers that reflect specific pathogenic mechanisms including neuroinflammation, oxidative damage, and neuroregeneration, in moderate-to-severe TBI patients.Materials and methodsPeripheral blood was drawn from 85 isolated TBI patients (n = 60 severe, n = 25 moderate) at hospital admission, 6-, 12-, and 24-h post-injury. Mortality and neurological outcome were assessed using the extended Glasgow Outcome Scale. A multiplex platform was designed on MULTI-SPOT® plates to simultaneously analyze human plasma levels of s100 calcium binding protein beta (s100B), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), brain-derived neurotrophic factor (BDNF), monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-5, and peroxiredoxin (PRDX)-6. Multivariable logistic regression and area under the receiver-operating characteristic curve (AUC) were used to evaluate both individual and combined predictive abilities of these markers for 6-month neurological outcome and mortality after TBI.ResultsUnfavorable neurological outcome was associated with elevations in s100B, GFAP, and MCP-1. Mortality was related to differences in six of the seven markers analyzed. Combined admission concentrations of s100B, GFAP, and MCP-1 were able to discriminate favorable versus unfavorable outcome (AUC = 0.83), and survival versus death (AUC = 0.87), although not significantly better than s100B alone (AUC = 0.82 and 0.86, respectively).ConclusionThe multi-marker panel of TBI-related biomarkers performed well in discriminating unfavorable and favorable outcomes in the acute period after moderate-to-severe TBI. However, the combination of these biomarkers did not outperform s100B alone.

Treatment of traumatic brain injury in rats with N-acetyl-seryl-aspartyl-lysyl-proline

“…A previous clinical study indicates that TBI patients who died within first 24 hours have a significantly higher GFAP concentration in the blood at 6, 12, and 24 hours after TBI, moreover, a high level of GFAP in blood was associated with poor outcome at 1–6 months. 19 …”

Blood biomarkers for brain injury: What are we measuring?

“…Previous reports have shown that this level can increase to nearly 5 ng/ml after severe TBI. Increased serum levels of S100β have been observed within 24 h of severe TBI and strongly correlate with a prognosis of mortality (Goyal et al, 2013; Korfias et al, 2007; Raabe et al, 1999; Rainey et al, 2009; Vos et al, 2004; Pelinka et al, 2004a; Di Battista et al, 2015). Similarly, S100β has been useful in predicting whether a patient would regain consciousness or remain unconscious 3–6 months post-injury.…”

“…The superiority of S100β as a prognostic biomarker for mortality and unfavorable outcomes was supported by a recent study using a multi-marker approach that included GFAP, NSE, brain-derived neurotrophic factor, and monocyte chemoattractant protein-1. While the combination of these markers discriminated mortality and outcome measures, S100β alone could predict poor prognosis after TBI equally well as the multi-marker panel (Di Battista et al, 2015). …”

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

“…Functionally, S100β inhibition reduced neurodegeneration [123] and S100β −/− mice or antibody-mediated neutralization of S100β attenuated microglial reactivity and improved memory function after experimental TBI [124]. Thus, S100β may represent a predictive biomarker of outcomes and target for therapeutic development after TBI [125]. …”