Evaluation of a Novel Therapy to Improve Recovery from Moderate Traumatic Brain Injury After Critical Care Air Transport Team (CCATT) Transport- Optimizing Advanced Point of Injury to En Route Care
Abstract
Traumatic brain injury (TBI) is a major health issue that is particularly relevant in active duty populations. TBI is often associated with long-term disabilities; predominantly reduced learning and memory, as well as anxiety and executive function. Therapies to improve survival and long-term outcomes following TBI suffered on the battlefield are scarce. Strategies to both reduce brain injury and improve functional activity of the brain following TBI are critically important for the advancement of therapies from the bench to bedside. Consideration of war time TBI requires the understanding of the fact that TBI is often suffered in locations that require transport to optimal trauma centers (CCATT). In this proposal we use our recently developed mouse model of traumatic brain injury combined with CCATT to determine the effect of treatment with our novel Transient Receptor Potential M2 (TRPM2) inhibitor (tat-M2NX) on functional outcome after TBI+CCATT. We have identified the oxidative-stress sensitive ion channel, TRPM2, as a novel mediator of TBI-induced cognitive dysfunction and a key contributor to TBI induced pathology. To confirm the functional benefit of acute inhibition of TRPM2 channels with tat-M2NX after TBI, we performed hippocampal-dependent neurobehavioral testing to measure memory function in mice 7 days after recovery from TBI. We found that that early pharmacological inhibition of TRPM2 channels with tat-M2NX provided sustained functional benefit. Our data indicates TRPM2 channel inhibition with tat-M2NX is a potential therapeutic during aeromedical transport for soldiers who have sustained TBI. The findings from our current study suggest that acute intervention at the time of CCATT is recommended and further development of our tat-M2NX is warranted.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2023
- Accession Number
- AD1208672
Entities
People
- Paco S Herson
- Vikhyat S Bebarta
Organizations
- University of Colorado