Molecular Signatures and Diagnostic Biomarkers of Cumulative Blast-Graded Mild TBI.

摘要

During grant the period, the PI established and standardized blast load characteristics produced by mild through severe TBI and defined 'composite' and primary blast parameters and brain injury signatures in these two blast modalities. Neuro-glial injury was evaluated by silver staining. GFAP and CNPase up-regulation in brain tissue was assessed by immunohistochemistry. The levels of biomarkers in biofluids were assessed by ELISA, antibody microarrays, and Western Blot. Single and repeated blast increased levels of selected biomarkers in a time dependent manner. Multiple blasts significantly augmented increased levels of GFAP, UCH-L1, CNPase, NSE, IL-1, IL-10, sICAM, L- and E-selectins, NSE and NRP-2, but not Orexin A, as compared to a single blast. In contrast, a low magnitude blast produced no significant effects on the levels of these biomarkers. We found and characterized new signatures of blast injuries: thrombin activity measured by calibrated activated thrombography (CAT), linked to microcirculation disorders following blast exposures. In addition, we developed, characterized and validated a portable cumulative blast detection device using novel MEMS chip technology (FIT).