Operation Brain Trauma Therapy: 2016 Update.

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.

• Authors: 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
• Journal: Military medicine (Mil Med) Vol. 183 Issue suppl_1 Pg. 303-312 (03 01 2018) ISSN: 1930-613X [Electronic] England
• PMID: 29635589 (Publication Type: Journal Article, Multicenter Study, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers
• GFAP protein, human
• Glial Fibrillary Acidic Protein
• UCHL1 protein, human
• Ubiquitin Thiolesterase

Topics

• Animals
• Biomarkers (blood)
• Brain Injuries, Traumatic (drug therapy)
• Cognition (drug effects)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay (methods)
• Glial Fibrillary Acidic Protein (analysis, blood)
• Mass Screening (methods, trends)
• Rats
• Rats, Sprague-Dawley (injuries)
• Recovery of Function (drug effects)
• Ubiquitin Thiolesterase (analysis, blood)