Related Experiment Video
Updated: Mar 28, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Synthesis of Findings, Current Investigations, and Future Directions: Operation Brain Trauma Therapy
Patrick M Kochanek1, Helen M Bramlett2,3, Deborah A Shear4
11 Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Abstract:
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.
Insights
Operation Brain Trauma Therapy (OBTT) screened multiple treatments for traumatic brain injury (TBI). Levetiracetam showed promise, while others underperformed, highlighting the need for rigorous pre-clinical TBI research.
Area of Science:
- Neuroscience
- Pharmacology
- Biomarker Research
Background:
- Traumatic brain injury (TBI) presents significant challenges in clinical translation of therapies.
- A rigorous, multicenter pre-clinical screening approach is crucial for advancing TBI treatment.
- Operation Brain Trauma Therapy (OBTT) was established to address these challenges.
Purpose of the Study:
- To synthesize findings from the first five therapies evaluated by OBTT.
- To discuss ongoing and future directions for TBI therapeutic development.
- To assess the utility of circulating biomarkers in pre-clinical TBI studies.
Main Methods:
- OBTT employs a rigorous, multicenter, pre-clinical drug screening consortium for TBI.
- Five therapies were initially tested, with subsequent evaluations of additional agents.
- Glial fibrillary acidic protein (GFAP) was incorporated as a circulating biomarker.
Main Results:
- Four of the first five therapies (nicotinamide, erythropoietin, cyclosporine A, simvastatin) did not meet expectations based on literature.
- Levetiracetam demonstrated promise as an early post-TBI treatment and advanced to a large animal model.
- Glial fibrillary acidic protein (GFAP) showed potential for diagnostic and theranostic applications in pre-clinical TBI models.
Conclusions:
- Rigorous pre-clinical screening consortia like OBTT are vital for successful TBI therapy translation.
- Levetiracetam represents a promising therapeutic candidate for TBI.
- Circulating biomarkers, such as GFAP, offer significant potential for TBI research and clinical application.
