The main function of an Academic Research Enhancement Award (AREA) is to stimulate meritorious research at primarily undergraduate institutions that are not major recipients of NIH support as mandated by the National Institutes of Health. Two additional objectives are to strengthen the research environment at such institutions and expose students in these environments to research. This research proposal fits all the objectives of this directive. The goal of this project is to evaluate the efficacy of gamma glutamylcysteine ethyl ester, a glutathione mimetic, as a post therapeutic strategy for moderate traumatic brain injury. Traumatic brain injury (TBI) is defined as a sudden trauma followed by secondary damage. It occurs in approximately 10 million people worldwide. There is no known cure for traumatic brain injury;however immediate medical attention after incident is most beneficial for patient recovery. Since TBI is a sudden injury, post therapeutic strategies are the only viable approach to therapy. Gamma glutamylcysteine ethyl ester (GCEE) is an ethyl ester moiety of gamma glutamylcysteine which upregulates glutathione (GSH), a potent antioxidant, in brain. Preliminary data from our laboratory show a significant reduction in oxidative stress levels when GCEE is administered 10 minutes post TBI;however, early management of injury is the best preventative measure of progressive secondary injury. This proposal will investigate a potential GSH-based therapeutic for TBI post injury at several time points (30 minutes, 60 minutes, 90 minutes, and 120 minutes) to determine the best time course of protection against secondary injury of TBI. The specific hypothesis is that GCEE administration is still neuroprotective at 30 minutes post injury and may possibly be neuroprotective at 60 minutes, 90 minutes, and 120 minutes post injury to a lesser extent. Should GCEE given post TBI be protective against TBI-induced secondary injury for longer than 10 minutes, this would be an effective intervention that could feasibly be administered in the field. Such an outcome would be highly beneficial for post-TBI modulation of secondary injury and recovery outcomes. This proposal would also contribute to increasing scientific knowledge in the field of traumatic brain injury research and create a strong research environment for students at Eastern Kentucky University. The funding of this AREA application will expand biomedical research for students and better enable students from Kentucky, a traditionally underrepresented state in biomedical sciences, to advance in biomedical graduate programs.
Approximately ten million people worldwide suffer from a traumatic brain injury (TBI) for which there is currently no therapeutic intervention. The proposed studies in this application would evaluate the pharmacological efficacy of gamma glutamylcysteine ethyl ester (GCEE) as a post therapeutic treatment and investigate its remediation of traumatic brain injury. The use of GCEE as a neuroprotective agent against oxidative stress in this TBI study would demonstrate the prevention of functional neurological decline and restoration of function following brain injury.
|Henderson, Moses; Rice, Brittany; Sebastian, Andrea et al. (2016) Neuroproteomic study of nitrated proteins in moderate traumatic brain injured rats treated with gamma glutamyl cysteine ethyl ester administration post injury: Insight into the role of glutathione elevation in nitrosative stress. Proteomics Clin Appl 10:1218-1224|