Biochemical Markers of Brain Injury: An Integrated Proteomics-Based Approach

Abstract : Brain injury poses a major problem to military care. Historically brain injury has accounted for 25% of all combat casualties and is the leading cause of death among wounded soldiers reaching Echelon I medical treatment. Recent experience in Iraq has suggested brain injury may make an even greater contribution to combat casualties. Incidence of brain injury and resultant long-term disabilities caused by traumatic insults and ischemic events is significantly greater in the civilian population. No clinically useful diagnostic tests exist for traumatic or ischemic brain injury to provide physicians with quantifiable neurochemical markers to help determine the seriousness of the injury, the anatomical and cellular pathology of the injury and to guide implementation of appropriate triage and medical management. Study Design: SOW 1 employs integrated proteomics-based technologies to identify specific proteins or peptide fragments in brain released into CSF and/or blood of rats following experimental traumatic brain injury or focal cerebral ischemia. Technologies include mass spectroscopy, 2-D gel electrophoresis, phage display of single chain antibodies and antibody chips. SOW 2 employs antibody chips to determine which proteins or peptide fragments released into CSF following injury are reliably associated with different injury magnitudes and predict changes in histopathological, behavioral and electrophysiological outcome measures. SOW 3 develops ELISA-based assays capable of detecting biomarkers in blood. Relevance: Development of "objective triage" capabilities for combat medics and/or Echelon I providers would represent a major "fieldable" breakthrough in the medical management of combat related head trauma.