학술논문

Operation Brain Trauma Therapy: 2016 Update.
Document Type
Journal Article
Source
Military Medicine. 2018 Supplement, Vol. 183, p303-312. 10p.
Subject
*BRAIN injury treatment
*TREATMENT effectiveness
*NERVOUS system injuries
*PROTEIN analysis
*TUMOR markers
*CLINICAL trials
*LABORATORY rats
*ANIMAL experimentation
*BIOLOGICAL models
*COGNITION
*COMPARATIVE studies
*CONVALESCENCE
*CYTOSKELETAL proteins
*ENZYME-linked immunosorbent assay
*ESTERASES
*RESEARCH methodology
*MEDICAL cooperation
*MEDICAL screening
*RATS
*RESEARCH
*EVALUATION research
Language
ISSN
0026-4075
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. [ABSTRACT FROM AUTHOR]