Operation Brain Trauma Therapy: 2016 Update

Patrick M. Kochanek, Helen M. Bramlett, C. Edward Dixon, W. Dalton Dietrich, Stefania Mondello, Kevin K.W. Wang, Ronald L. Hayes, Audrey Lafrenaye, John T. Povlishock, Frank C. Tortella, Samuel M. Poloyac, Philip Empey, Deborah A. Shear

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Operation 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.

Original languageEnglish (US)
Pages (from-to)303-312
Number of pages10
JournalMilitary medicine
Volume183
DOIs
StatePublished - Mar 1 2018

Keywords

  • Biomarker
  • Consortium
  • Multi-center
  • Rat
  • Rigor
  • Therapy
  • Traumatic brain injury

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

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    Kochanek, P. M., Bramlett, H. M., Dixon, C. E., Dietrich, W. D., Mondello, S., Wang, K. K. W., Hayes, R. L., Lafrenaye, A., Povlishock, J. T., Tortella, F. C., Poloyac, S. M., Empey, P., & Shear, D. A. (2018). Operation Brain Trauma Therapy: 2016 Update. Military medicine, 183, 303-312. https://doi.org/10.1093/milmed/usx184