Rapid Evaluation of a Blood Biomarker of Traumatic Brain Injury

Currently, traumatic brain injury (TBI) is a substantial health care issue affecting both civilian and military populations. In the US ~1.5 to 2 million civilians/year suffer TBI primarily through falls, motor vehicle accidents and sports related injuries. Although extremes of head injury are recognizable, mild TBI (mTBI) is more difficult to diagnose. Current in-hospital screening for TBI includes radiographic scans (non-contrast CT and MRI) and determination of the Glasgow Coma Score. Although non-contrast CT is generally available and is useful for detection of acute hemorrhage and fracture associated with severe trauma, it is less sensitive for diffuse injury associated with mTBI. Because of the need for more rapid, pre-hospital identification of subjects with TBI study has turned to the quantification of circulating biomarkers of brain injury that may facilitate early identification. Current studies of biomarkers of TBI have focused on levels of multiple brain related including creatine kinase, glial filament associated protein (GFAP), myelin basic protein (MBP), neuron specific enolase (NSE) and s100ß protein that may be quantified in blood or cerebrospinal fluid (CSF). Unfortunately, the markers have been quantified using enzyme linked immunoassays (ELISAs) that are temperature sensitive and can take as long as 12 – 16 hours to complete which is well beyond a therapeutically beneficial window. More recent studies suggest that current blood biomarkers are not sufficiently sensitive and specific for the identification of mTBI. In preliminary studies we identified a novel protein, visinin like protein- 1 (VILIP-1), a neuron specific protein that is released into blood following neuronal injury. To facilitate rapid analysis of levels of VILIP-1 we developed a vertical/lateral flow device that combines a cell removal membrane and a nano-gold detection antibody to quantify levels of VILIP-1 in less than 10 minutes. The device is stable at room temperature and may be useful for in-field analysis. Based on our preliminary data we propose to test the hypothesis that use of a lateral flow device to quantify VILIP-1 in blood will allow delineation of mild, moderate and severe TBI. If successful, the proposed studies will confirm the efficacy of quantification of VILIP-1 in the rapid identification of mTBI allowing quicker treatment.