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

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.

Beta-blockers and Traumatic Brain Injury

“…brain injury severity, polytrauma, associated co-morbidities, daily ICU events) to reveal effects on long-term patient-centered outcomes on cognition, neurologic function, and quality of life. Given the complexity of TBI management as well as subtle possible differences in clinical signs and symptoms, imaging, and genetic variances in the population, a large federally supported trauma consortium should provide the funding and research infrastructure necessary to advance the field in this regard (75). …”

Rethinking Neuroprotection in Severe Traumatic Brain Injury: Toward Bedside Neuroprotection

“…In recent years, new approaches and research strategies have been proposed (19–21) to overcome these obstacles (see Panel). Operation Brain Trauma Therapy (21) moves in this direction.…”

“…Operation Brain Trauma Therapy (21) moves in this direction. OBTT is a consortium of established preclinical TBI investigators supported by the US Army.…”

Argon attenuates the emergence of secondary injury after traumatic brain injury within a 2-hour incubation period compared to desflurane: an in vitro study

“…Total annual cost for TBI was estimated to be €33 billion (direct health care costs, direct non-medical costs and indirect costs). Until now, treatment of TBI remains difficult due to the multitude of trauma mechanisms and the limited knowledge of pathological pathways 678…”