PMID- 25870583 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150414 LR - 20220311 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 6 DP - 2015 TI - Multivariate analysis of traumatic brain injury: development of an assessment score. PG - 68 LID - 10.3389/fneur.2015.00068 [doi] LID - 68 AB - Important challenges for the diagnosis and monitoring of mild traumatic brain injury (mTBI) include the development of plasma biomarkers for assessing neurologic injury, monitoring pathogenesis, and predicting vulnerability for the development of untoward neurologic outcomes. While several biomarker proteins have shown promise in this regard, used individually, these candidates lack adequate sensitivity and/or specificity for making a definitive diagnosis or identifying those at risk of subsequent pathology. The objective for this study was to evaluate a panel of six recognized and novel biomarker candidates for the assessment of TBI in adult patients. The biomarkers studied were selected on the basis of their relative brain-specificities and potentials to reflect distinct features of TBI mechanisms including (1) neuronal damage assessed by neuron-specific enolase (NSE) and brain derived neurotrophic factor (BDNF); (2) oxidative stress assessed by peroxiredoxin 6 (PRDX6); (3) glial damage and gliosis assessed by glial fibrillary acidic protein and S100 calcium binding protein beta (S100b); (4) immune activation assessed by monocyte chemoattractant protein 1/chemokine (C-C motif) ligand 2 (MCP1/CCL2); and (5) disruption of the intercellular adhesion apparatus assessed by intercellular adhesion protein-5 (ICAM-5). The combined fold-changes in plasma levels of PRDX6, S100b, MCP1, NSE, and BDNF resulted in the formulation of a TBI assessment score that identified mTBI with a receiver operating characteristic (ROC) area under the curve of 0.97, when compared to healthy controls. This research demonstrates that a profile of biomarker responses can be used to formulate a diagnostic score that is sensitive for the detection of mTBI. Ideally, this multivariate assessment strategy will be refined with additional biomarkers that can effectively assess the spectrum of TBI and identify those at particular risk for developing neuropathologies as consequence of a mTBI event. FAU - Buonora, John E AU - Buonora JE AD - Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA ; U.S. Army Graduate Program in Anesthesia Nursing, Academy of Health Sciences, Joint Base San Antonio , Fort Sam Houston, TX , USA. FAU - Yarnell, Angela M AU - Yarnell AM AD - Behavioral Biology Branch, Center for Military Psychiatry and Neuroscience Research, Walter Reed Army Institute of Research , Silver Spring, MD , USA. FAU - Lazarus, Rachel C AU - Lazarus RC AD - Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA. FAU - Mousseau, Michael AU - Mousseau M AD - Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA. FAU - Latour, Lawrence L AU - Latour LL AD - Stroke Branch, National Institute of Neurological Disorders and Stroke , Bethesda, MD , USA ; Defence Research and Development Canada, Toronto Research Centre , Toronto, ON , Canada. FAU - Rizoli, Sandro B AU - Rizoli SB AD - Department of Anesthesia, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto , Toronto, ON , Canada ; Department of Surgery, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto , Toronto, ON , Canada ; Department of Critical Care Medicine, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto , Toronto, ON , Canada. FAU - Baker, Andrew J AU - Baker AJ AD - Department of Anesthesia, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto , Toronto, ON , Canada ; Department of Surgery, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto , Toronto, ON , Canada ; Department of Critical Care Medicine, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto , Toronto, ON , Canada ; Brain Injury Laboratory, Li Ka Shing Knowledge Institute, Cara Phelan Centre for Trauma Research, Keenan Research Centre University of Toronto , Toronto, ON , Canada. FAU - Rhind, Shawn G AU - Rhind SG AD - Defence Research and Development Canada, Toronto Research Centre , Toronto, ON , Canada. FAU - Diaz-Arrastia, Ramon AU - Diaz-Arrastia R AD - Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD , USA. FAU - Mueller, Gregory P AU - Mueller GP AD - Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA. LA - eng PT - Journal Article DEP - 20150330 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC4378282 OTO - NOTNLM OT - assessment score OT - biomarkers OT - human OT - mild traumatic brain injury OT - multivariate analysis EDAT- 2015/04/15 06:00 MHDA- 2015/04/15 06:01 PMCR- 2015/03/30 CRDT- 2015/04/15 06:00 PHST- 2015/01/14 00:00 [received] PHST- 2015/03/12 00:00 [accepted] PHST- 2015/04/15 06:00 [entrez] PHST- 2015/04/15 06:00 [pubmed] PHST- 2015/04/15 06:01 [medline] PHST- 2015/03/30 00:00 [pmc-release] AID - 10.3389/fneur.2015.00068 [doi] PST - epublish SO - Front Neurol. 2015 Mar 30;6:68. doi: 10.3389/fneur.2015.00068. eCollection 2015.