title: Blood Biomarkers in Moderate-To-Severe Traumatic Brain Injury: Potential Utility of a Multi-Marker Approach in Characterizing Outcome.
abstract: BACKGROUND
  Blood 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.
  
  
  METHODS
  Peripheral 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.
  
  
  RESULTS
  Unfavorable 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Faculty of Medicine, Institute of Medical Science, University of Toronto , Toronto, ON , Canada ; Defence Research and Development Canada, Toronto Research Centre , Toronto, ON , Canada ; Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital , Toronto, ON , Canada.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Di Battista
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA ; US Army Graduate Program in Anesthesia Nursing , Fort Sam Houston, TX , USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Buonora
authors.affiliation: Defence Research and Development Canada, Toronto Research Centre , Toronto, ON , Canada ; Faculty of Kinesiology and Physical Education, David L. MacIntosh Sport Medicine Clinic, University of Toronto , Toronto, ON , Canada.
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Rhind
authors.affiliation: Faculty of Kinesiology and Physical Education, David L. MacIntosh Sport Medicine Clinic, University of Toronto , Toronto, ON , Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hutchison
authors.affiliation: Faculty of Medicine, Institute of Medical Science, University of Toronto , Toronto, ON , Canada ; Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital , Toronto, ON , Canada ; Department of Anesthesia, University of Toronto , Toronto, ON , Canada ; Department of Surgery and Critical Care Medicine, University of Toronto , Toronto, ON , Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baker
authors.affiliation: Faculty of Medicine, Institute of Medical Science, University of Toronto , Toronto, ON , Canada ; Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital , Toronto, ON , Canada ; Department of Anesthesia, University of Toronto , Toronto, ON , Canada ; Department of Surgery and Critical Care Medicine, University of Toronto , Toronto, ON , Canada.
authors.forename: Sandro B
authors.initials: SB
authors.lastname: Rizoli
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Mueller
keywords: BDNF; GFAP; ICAM-5; MCP-1; NSE; PRDX-6; s100B