Treatment of traumatically brain injured rats with gamma glutamylcysteine ethyl e

描述（由申请人提供）：学术研究增强奖（AREA）的主要功能是激励主要本科院校的有价值的研究，这些院校不是美国国立卫生研究院（NIH）支持的主要接受者。另外两个目标是加强这些机构的研究环境，并使这些环境中的学生接触研究。这项研究计划符合该指令的所有目标。本项目的目的是评估γ-谷氨酰半胱氨酸乙酯（一种谷胱甘肽模拟物）作为中度创伤性脑损伤后治疗策略的疗效。创伤性脑损伤（TBI）是指突发性脑外伤后继发性脑损伤。它发生在全世界约1000万人。创伤性脑损伤没有已知的治愈方法;然而，事件发生后立即进行医疗护理对患者恢复最有益。由于TBI是一种突发性损伤，治疗后策略是唯一可行的治疗方法。γ-谷氨酰半胱氨酸乙酯（GCEE）是γ-谷氨酰半胱氨酸的乙酯部分，其上调脑中的谷胱甘肽（GSH），一种有效的抗氧化剂。我们实验室的初步数据显示，TBI后10分钟给予GCEE时，氧化应激水平显著降低;然而，损伤的早期管理是进行性继发性损伤的最佳预防措施。该提案将在几个时间点（30分钟、60分钟、90分钟和120分钟）研究TBI损伤后的潜在GSH基治疗剂，以确定保护免受TBI继发性损伤的最佳时间过程。具体的假设是，GCEE给药在损伤后30分钟仍然具有神经保护作用，并且可能在损伤后60分钟、90分钟和120分钟具有较低程度的神经保护作用。如果在TBI后给予GCEE对TBI诱导的继发性损伤具有保护作用超过10分钟，这将是一种有效的干预措施，可以在现场进行可行的管理。这样的结果将非常有益于TBI后继发性损伤和恢复结果的调节。该提案还将有助于增加创伤性脑损伤研究领域的科学知识，并为东肯塔基州大学的学生创造一个强大的研究环境。该地区申请的资金将扩大学生的生物医学研究，并更好地使学生从肯塔基州，一个传统上代表性不足的国家在生物医学科学，推进生物医学研究生课程。 公共卫生相关性：全世界大约有一千万人患有创伤性脑损伤（TBI），目前没有治疗干预。本申请中拟定的研究将评价γ-谷氨酰半胱氨酸乙酯（GCEE）作为治疗后治疗的药理学疗效，并研究其对创伤性脑损伤的修复作用。在该TBI研究中使用GCEE作为抗氧化应激的神经保护剂将证明预防脑损伤后的功能性神经功能下降和功能恢复。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.