The Office of Naval Research has awarded Duke Anesthesiology’s Heath Gasier, PhD, a three-year $844,714 grant for his project titled, “The Role of GABA in Susceptibility to Oxygen Toxicity with Repeated HB02 Exposure.”
Hyperbaric oxygen (HBO2) increases the partial pressure of oxygen (PO2) in the lungs, blood and tissues. The pulmonary and central nervous systems are very sensitive to changes in PO2, and high levels can cause oxidant tissue damage that can be lethal. The United States Navy established single-depth oxygen exposure limits that serve to reduce the probability of developing central nervous system oxygen toxicity (CNS-OT), thus are restrictive for depth and time. For this reason, research has been directed towards understanding the mechanisms of CNS-OT with the goal of finding targeted prevention strategies.
Gasier’s research will determine the role of GABAergic transmission in modulating repeated HBO2 exposure sensitivity to CNS- and pulmonary-OT. This study addresses four significant questions: 1) is the increased sensitivity to repeated HBO2 exposures due to inadequate recovery from oxidant tissue damage? 2) In female mice, are progesterone and estrogen related to GABA levels and susceptibility to CNS-OT? 3) Is the reduction in GABA concentration contributing to oxidant lung injury? 4) Does increasing the GABA-to-glutamate ratio by administration of TGB decrease repeated HBO2 exposure sensitivity to oxidant tissue damage? This study will also determine whether increasing GABA levels impact exercise performance after HBO2.
Data collected from this work will improve the understanding of the mechanisms of CNS- and pulmonary-OT, and open opportunities for new prevention strategies. More importantly, it will lay the groundwork for conducting efficacy studies in humans.