Weber & Maas (Eds.) Progress in Brain Research, Vol. 161 ISSN 0079-6123 Copyright r 2007 Elsevier B.V. All rights reserved Novel neuroproteomic approaches to studying traumatic brain injury Andrew K. Ottens 1,2,Ã , Firas H. Kobeissy 1,2 , Brian F. Fuller 1,2 , Ming Chen Liu 1,2 , Monika W. Oli 3 , Ronald L. Hayes 2,3 and Kevin K.W. Wang 1,2,3 1 Departments QA :1 of Psychiatry and Neuroscience, Center for Neuroproteomics and Biomarkers Research at the Evelyn F. and William L. McKnight Brain Institute of the University of Florida, Gainesville, FL 32610, USA 2 Departments of Neurosurgery and Clinical and Health Psychology, Center for Traumatic Brain Injury Studies at the Evelyn F. and William L. McKnight Brain Institute of the University of Florida, Gainesville, FL 32610, USA 3 Banyan Biomarkers, Inc., 12085 Research Dr., Alachua, FL 32615, USA Abstract: Neuroproteomics QA :2 entails wide-scope study of the nervous system proteome in both its content and dynamics. The field employs high-end analytical mass spectrometry and novel high-throughput an- tibody approaches to characterize as many proteins as possible. The most common application has been differential analysis to identify a limited set of highly dynamic proteins associated with injury, disease, or other altered states of the nervous system. Traumatic brain injury (TBI) is an important neurological condition where neuroproteomics has revolutionized the characterization of protein dynamics, leading to a greater understanding of post-injury biochemistry. Further, proteins of altered abundance or post-trans- lational modifications identified by neuroproteomic studies are candidate biochemical markers of TBI. This chapter explores the use of neuroproteomics in the study of TBI and the validation of identified putative biomarkers for subsequent clinical translation into novel injury diagnostics. Introduction to TBI Traumatic brain injury (TBI) is neurotrauma caused by a mechanical force applied to the head (Wang et al., 2004). There are approximately 1.4–2 million TBI incidents annually in the United States, resulting in 1.1 million emergency depart- ment visits, 235,000 hospitalizations, 90,000 left with long-term disabilities, and 50,000 deaths (La- nglois et al., 2006b; Ragnarsson, 2006). Yet the true burden of TBI may not be reflected in these numbers as many TBI incidents go unreported or are not classified as TBI. For example it is estimated that between 1.6 and 3.8 million sports-related TBI incidents actually occur in the US as compared with the 300,000 reported. TBI costs the American economy an estimated $60 bil- lion per year in medical expenses and lost produc- tivity (Finkelstein et al., 2006). All told, TBI represents a major public health problem with sig- nificant societal and economic consequences (So- sin et al., 1995; Wang et al., 2004; Yi and Hazell, 2006). Despite this, there remains no approved therapy for TBI (Narayan et al., 2002; Wieloch and Nikolich, 2006). TBI results from a number of etiologies (Fig. 1) primarily effecting male (78.8% of incidents) ad- olescents and young adults (31.7% of incidents are among 15- to 24-year olds). In fact, TBI is 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 3B2v8:06a=w ðDec 5 2003Þ:51c XML:ver:5:0:1 PBR À V161 : 61029 Prod:Type: pp:3952412ðcol:fig::NILÞ ED: PAGN: SCAN: Ã Corresponding author. Tel.: +352-392-8060; Fax: +352-392- 2579; E-mail: aottens@mbi.ufl.edu DOI: 10.1016/S0079-6123(06)61029-7 395