Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcome

Background: Blood biomarkers are valuable tools for elucidating the complex cellular and molecular mechanisms underlying traumatic brain injury (TBI) pathophysiology. Profiling distinct classes of biomarkers could aid in the identification and characterization of both initial injury and secondary pa...

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Main Authors: Alex P Di Battista, John E Buonora, Shawn G Rhind, Michael Gary Hutchison, Andrew J Baker, Sandro B. Rizoli, Ramon eDiaz-Arrastia, Gregory P Mueller
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-05-01
Series:Frontiers in Neurology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fneur.2015.00110/full
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author Alex P Di Battista
Alex P Di Battista
Alex P Di Battista
John E Buonora
Shawn G Rhind
Shawn G Rhind
Michael Gary Hutchison
Andrew J Baker
Andrew J Baker
Andrew J Baker
Sandro B. Rizoli
Sandro B. Rizoli
Ramon eDiaz-Arrastia
Gregory P Mueller
author_facet Alex P Di Battista
Alex P Di Battista
Alex P Di Battista
John E Buonora
Shawn G Rhind
Shawn G Rhind
Michael Gary Hutchison
Andrew J Baker
Andrew J Baker
Andrew J Baker
Sandro B. Rizoli
Sandro B. Rizoli
Ramon eDiaz-Arrastia
Gregory P Mueller
author_sort Alex P Di Battista
collection DOAJ
description Background: Blood biomarkers are valuable tools for elucidating the complex cellular and molecular mechanisms underlying traumatic brain injury (TBI) pathophysiology. Profiling distinct classes of biomarkers could aid in the identification and characterization of both initial injury and secondary pathological processes. The purpose of this study was to characterize the prognostic performance, both individually and combined, of a recently developed multimarker panel of circulating biomarkers reflecting specific pathogenic mechanisms including neuroinflammation, oxidative damage and neuroregeneration, in moderate-to-severe TBI patients. Materials and Methods: Peripheral blood samples were 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 Score (GOSE). A multiplex platform was designed on MULTI-SPOT® plates to simultaneously analyze human plasma levels of s100 calcium binding protein (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. Results: Unfavorable outcome was associated with elevations in s100B, GFAP and MCP-1. Mortality was related to differences in 6 of 7 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). Conclusion: The multimarker panel of TBI-related biomarkers performed well in discriminating between unfavorable and favorable outcomes in the acute period after moderate-to-severe TBI. However, these combined biomarkers did not outperform s100B alone.
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spelling doaj.art-8213791852d542c9bdec4fef6ae623f52022-12-21T18:57:57ZengFrontiers Media S.A.Frontiers in Neurology1664-22952015-05-01610.3389/fneur.2015.00110145046Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcomeAlex P Di Battista0Alex P Di Battista1Alex P Di Battista2John E Buonora3Shawn G Rhind4Shawn G Rhind5Michael Gary Hutchison6Andrew J Baker7Andrew J Baker8Andrew J Baker9Sandro B. Rizoli10Sandro B. Rizoli11Ramon eDiaz-Arrastia12Gregory P Mueller13University of TorontoSt. Michael's HospitalDefence Research and Development CanadaUniformed Services University of the Health SciencesDefence Research and Development CanadaUniversity of TorontoUniversity of TorontoUniversity of TorontoSt. Michael's HospitalUniversity of TorontoSt. Michael's HospitalUniversity of TorontoUniformed Services University of the Health SciencesUniformed Services University of the Health SciencesBackground: Blood biomarkers are valuable tools for elucidating the complex cellular and molecular mechanisms underlying traumatic brain injury (TBI) pathophysiology. Profiling distinct classes of biomarkers could aid in the identification and characterization of both initial injury and secondary pathological processes. The purpose of this study was to characterize the prognostic performance, both individually and combined, of a recently developed multimarker panel of circulating biomarkers reflecting specific pathogenic mechanisms including neuroinflammation, oxidative damage and neuroregeneration, in moderate-to-severe TBI patients. Materials and Methods: Peripheral blood samples were 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 Score (GOSE). A multiplex platform was designed on MULTI-SPOT® plates to simultaneously analyze human plasma levels of s100 calcium binding protein (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. Results: Unfavorable outcome was associated with elevations in s100B, GFAP and MCP-1. Mortality was related to differences in 6 of 7 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). Conclusion: The multimarker panel of TBI-related biomarkers performed well in discriminating between unfavorable and favorable outcomes in the acute period after moderate-to-severe TBI. However, these combined biomarkers did not outperform s100B alone.http://journal.frontiersin.org/Journal/10.3389/fneur.2015.00110/fullBDNFGFAPS100BMCP-1NSEICAM-5
spellingShingle Alex P Di Battista
Alex P Di Battista
Alex P Di Battista
John E Buonora
Shawn G Rhind
Shawn G Rhind
Michael Gary Hutchison
Andrew J Baker
Andrew J Baker
Andrew J Baker
Sandro B. Rizoli
Sandro B. Rizoli
Ramon eDiaz-Arrastia
Gregory P Mueller
Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcome
Frontiers in Neurology
BDNF
GFAP
S100B
MCP-1
NSE
ICAM-5
title Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcome
title_full Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcome
title_fullStr Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcome
title_full_unstemmed Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcome
title_short Blood biomarkers in moderate-to-severe traumatic brain injury: potential utility of a multimarker approach in characterizing outcome
title_sort blood biomarkers in moderate to severe traumatic brain injury potential utility of a multimarker approach in characterizing outcome
topic BDNF
GFAP
S100B
MCP-1
NSE
ICAM-5
url http://journal.frontiersin.org/Journal/10.3389/fneur.2015.00110/full
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