Approach to Modeling, Therapy Evaluation, Drug Selection, and Biomarker Assessments for a Multicenter Pre-Clinical Drug Screening Consortium for Acute Therapies in Severe Traumatic Brain Injury: Operation Brain Trauma Therapy

Patrick M. Kochanek, Helen M. Bramlett, C. Edward Dixon, Deborah A. Shear, W. Dalton Dietrich, Kara E. Schmid, Stefania Mondello, Kevin K.W. Wang, Ronald L. Hayes, John T. Povlishock, Frank C. Tortella

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Traumatic brain injury (TBI) was the signature injury in both the Iraq and Afghan wars and the magnitude of its importance in the civilian setting is finally being recognized. Given the scope of the problem, new therapies are needed across the continuum of care. Few therapies have been shown to be successful. In severe TBI, current guidelines-based acute therapies are focused on the reduction of intracranial hypertension and optimization of cerebral perfusion. One factor considered important to the failure of drug development and translation in TBI relates to the recognition that TBI is extremely heterogeneous and presents with multiple phenotypes even within the category of severe injury. To address this possibility and attempt to bring the most promising therapies to clinical trials, we developed Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug screening consortium for acute therapies in severe TBI. OBTT was developed to include a spectrum of established TBI models at experienced centers and assess the effect of promising therapies on both conventional outcomes and serum biomarker levels. In this review, we outline the approach to TBI modeling, evaluation of therapies, drug selection, and biomarker assessments for OBTT, and provide a framework for reports in this issue on the first five therapies evaluated by the consortium.

Original languageEnglish (US)
Pages (from-to)513-522
Number of pages10
JournalJournal of neurotrauma
Volume33
Issue number6
DOIs
StatePublished - Mar 15 2016

Keywords

  • biomarker
  • controlled cortical impact
  • fluid percussion
  • micropig
  • neuroprotection
  • penetrating ballistic-like brain injury
  • rat
  • therapy

ASJC Scopus subject areas

  • Clinical Neurology

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