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Treatment of traumatically brain injured rats with gamma glutamylcysteine ethyl e

γ-谷氨酰半胱氨酸乙酯治疗脑外伤大鼠

基本信息

批准号：
8232580
负责人：
Tanea Tylette Reed
金额：
$ 39.42万
依托单位：
EASTERN KENTUCKY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8232580
关键词：
3-nitrotyrosine ATP Synthesis Pathway Academic Research Enhancement Awards Affect Aftercare Alkenes Animals Antioxidants Biological Assay Biomedical Research Brain Brain Injuries Data Electrophoresis Environment Enzymes Esters Funding Glutathione Glutathione Disulfide Glutathione Reductase Glutathione S-Transferase Goals Health Hippocampus (Brain)Injury Institution Kentucky Knowledge Laboratories Mass Spectrum Analysis Measurement Measures Mitochondria Modification Neurologic Neurons Neuroprotective Agents Nitrates Outcome Oxidative Stress Patients Prevention Proteins Proteomics Rattus Recovery Reduced Glutathione Research Research Proposals Role Sampling Science Staining method Stains Students System Techniques Testing Therapeutic Therapeutic Intervention Time Trauma Traumatic Brain Injury United States National Institutes of Health Universities Wistar Rats base effective intervention glutathione peroxidase injured medical attention mimetics mitochondrial dysfunction neuroprotection nitration programs protein profiling remediation restoration

项目摘要

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.

描述(由申请者提供)：学术研究促进奖(AREA)的主要功能是激励主要是本科生机构的有价值的研究，这些机构不是国家卫生研究院规定的主要接受NIH资助的机构。另外两个目标是加强这些机构的研究环境，并让这些环境中的学生接触研究。这项研究建议符合本指令的所有目标。该项目的目标是评估谷氨酰半胱氨酸乙酯，一种谷胱甘肽的模拟物，作为中度创伤性脑损伤的治疗后策略的疗效。创伤性脑损伤被定义为一种突发性创伤，继发于继发性损伤。全世界大约有1000万人患有这种疾病。目前尚无治愈创伤性脑损伤的方法，但伤后立即就医最有利于患者的康复。由于脑外伤是一种突发性损伤，治疗后的策略是唯一可行的治疗方法。谷氨酰半胱氨酸乙酯(GCEE)是谷氨酰半胱氨酸乙酯的一部分，它能上调大脑中一种有效的抗氧化剂谷胱甘肽(GSH)。我们实验室的初步数据显示，当在脑损伤后10分钟给予GCEE时，氧化应激水平显著降低；然而，早期处理损伤是进行性继发性损伤的最佳预防措施。这项建议将在几个时间点(30分钟、60分钟、90分钟和120分钟)研究一种潜在的基于GSH的治疗方法，以防止颅脑损伤后的继发性损伤。具体的假设是，GCEE在损伤后30分钟仍然具有神经保护作用，在损伤后60分钟、90分钟和120分钟可能具有较小程度的神经保护作用。如果颅脑损伤后给予GCEE的保护作用超过10分钟，这将是一种有效的干预措施，可以在现场可行地实施。这样的结果将非常有利于脑外伤后对继发性损伤和恢复结果的调整。这项提议还将有助于增加创伤性脑损伤研究领域的科学知识，并为东肯塔基大学的学生创造一个强有力的研究环境。这一领域申请的资金将扩大学生的生物医学研究，并更好地使来自肯塔基州的学生在生物医学研究生项目中取得进步。肯塔基州传统上是生物医学科学中代表性较低的州。公共卫生相关性：全球约有1000万人患有创伤性脑损伤，目前尚无治疗干预措施。这项拟议的研究将评估谷氨酰半胱氨酸乙酯(GCEE)作为治疗后治疗的药理作用，并探讨其对创伤性脑损伤的补救作用。在本研究中，使用GCEE作为对抗氧化应激的神经保护剂将证明GCEE可以预防脑损伤后功能性神经功能下降和功能恢复。