Synthesis of Findings, Current Investigations, and Future Directions: Operation Brain Trauma Therapy

Autor: Ronald L. Hayes, Helen M. Bramlett, Frank C. Tortella, Deborah A. Shear, Philip E. Empey, Kevin K.W. Wang, Patrick M. Kochanek, Travis C. Jackson, Steven P. Richieri, Olena Glushakova, Megan Browning, Ying Deng-Bryant, C. Edward Dixon, Samuel M. Poloyac, John T. Povlishock, Andrea Mountney, Michael Catania, Hong Q. Yan, Stefania Mondello, W. Dalton Dietrich
Rok vydání: 2015
Předmět:
Male
0301 basic medicine
Drug
medicine.medical_specialty
Neurology
Traumatic brain injury
media_common.quotation_subject
Drug Evaluation
Preclinical
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Brain Injuries
Traumatic
medicine
Animals
biomarker
controlled cortical impact
drug
fluid percussion
micropig
penetrating ballistic-like brain injury
pre-clinical modeling
rat
reproducibility
therapy
traumatic brain injury
Neurology (clinical)
rat
Intensive care medicine
Brain trauma
reproducibility
media_common
therapy
business.industry
fluid percussion
traumatic brain injury
drug
medicine.disease
Rats
Surgery
Disease Models
Animal
Circulating biomarkers
pre-clinical modeling
Neuroprotective Agents
030104 developmental biology
Erythropoietin
Biomarker (medicine)
biomarker
Levetiracetam
micropig
Neurology (clinical)
penetrating ballistic-like brain injury
business
controlled cortical impact
030217 neurology & neurosurgery
medicine.drug
Popis: Operation Brain Trauma Therapy (OBTT) is a fully operational, rigorous, and productive multicenter, pre-clinical drug and circulating biomarker screening consortium for the field of traumatic brain injury (TBI). In this article, we synthesize the findings from the first five therapies tested by OBTT and discuss both the current work that is ongoing and potential future directions. Based on the results generated from the first five therapies tested within the exacting approach used by OBTT, four (nicotinamide, erythropoietin, cyclosporine A, and simvastatin) performed below or well below what was expected based on the published literature. OBTT has identified, however, the early post-TBI administration of levetiracetam as a promising agent and has advanced it to a gyrencephalic large animal model--fluid percussion injury in micropigs. The sixth and seventh therapies have just completed testing (glibenclamide and Kollidon VA 64), and an eighth drug (AER 271) is in testing. Incorporation of circulating brain injury biomarker assessments into these pre-clinical studies suggests considerable potential for diagnostic and theranostic utility of glial fibrillary acidic protein in pre-clinical studies. Given the failures in clinical translation of therapies in TBI, rigorous multicenter, pre-clinical approaches to therapeutic screening such as OBTT may be important for the ultimate translation of therapies to the human condition.
Databáze: OpenAIRE
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