• Patrick M Kochanek, Helen M Bramlett, C Edward Dixon, W Dalton Dietrich, Stefania Mondello, WangKevin K WKKWProgram for Neuroproteomics and Biomarkers Research, Departments of Psychiatry, Neuroscience, and Chemistry, University of Florida, P.O. Box 100256, Gainesville, FL 32611., Ronald L Hayes, Audrey Lafrenaye, John T Povlishock, Frank C Tortella, Samuel M Poloyac, Philip Empey, and Deborah A Shear.
• Safar Center for Resuscitation Research, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224.
• Mil Med. 2018 Mar 1; 183 (suppl_1): 303-312.

AbstractOperation brain trauma therapy (OBTT) is a multi-center, pre-clinical drug and biomarker screening consortium for traumatic brain injury (TBI). Therapies are screened across three rat models (parasagittal fluid percussion injury, controlled cortical impact [CCI], and penetrating ballistic-like brain injury). Operation brain trauma therapy seeks to define therapies that show efficacy across models that should have the best chance in randomized clinical trials (RCTs) and/or to define model-dependent therapeutic effects, including TBI protein biomarker responses, to guide precision medicine-based clinical trials in targeted pathologies. The results of the first five therapies tested by OBTT (nicotinamide, erythropoietin, cyclosporine [CsA], simvastatin, and levetiracetam) were published in the Journal of Neurotrauma. Operation brain trauma therapy now describes preliminary results on four additional therapies (glibenclamide, kollidon-VA64, AER-271, and amantadine). To date, levetiracetam was beneficial on cognitive outcome, histology, and/or biomarkers in two models. The second most successful drug, glibenclamide, improved motor function and histology in CCI. Other therapies showed model-dependent effects (amantadine and CsA). Critically, glial fibrillary acidic protein levels predicted treatment effects. Operation brain trauma therapy suggests that levetiracetam merits additional pre-clinical and clinical evaluation and that glibenclamide and amantadine merit testing in specific TBI phenotypes. Operation brain trauma therapy has established that rigorous, multi-center consortia could revolutionize TBI therapy and biomarker development.

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