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Chronic TBI Bcl 2-20:34 Protection Against Lowered Seizure Susceptibility

慢性 TBI Bcl 2-20:34 预防癫痫易感性降低

基本信息

批准号：
8394619
负责人：
ROI Ann WALLIS
金额：
--
依托单位：
VA GREATER LOS ANGELES HEALTHCARE SYSTEM
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：
2011-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8394619
关键词：
Acute Adult American BCL-2 Protein BCL2 gene Behavioral Biochemical Biomechanics Brain Brain Injuries Cause of Death Cell Nucleus Cells Charge Chronic Complication Craniocerebral Trauma Development Epilepsy Experimental Models Generations Healthcare Hippocampus (Brain)In Vitro Injection of therapeutic agent Injury Lateral Lead Learning Left Life Long-Term Potentiation Longevity Magnesium Membrane Memory Memory Loss Mitochondria Mitochondrial Swelling Modeling Morbidity - disease rate Neurons Pathologic Pathway interactions Patients Peptides Perforant Pathway Persons Physiologic pulse Physiological Picrotoxin Play Post-Traumatic Epilepsy Predisposition Production Protein Binding Psychosocial Influences Pyramidal Cells Rattus Reactive Oxygen Species Recurrence Regulation Respiration Risk Role Seizures Site Slice Societies Structure Sudden Death Survivors Techniques Temporal Lobe Temporal Lobe Epilepsy Time Trauma Traumatic Brain Injury Veterans brain cell combat controlled cortical impact dentate gyrus granule cell hippocampal cell loss hippocampal subregions improved in vivo injured male mortality outcome forecast prevent public health relevance research study treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Traumatic Brain Injury (TBI) is a frequent combat injury. Unfortunately, survivors of head trauma may go on later to develop recurrent seizures. This problem, termed post-traumatic epilepsy, is associated with significant morbidity and mortality. The most common form of post-traumatic epilepsy originates in the hippocampus of the temporal lobe. Up to one third of such patients have medically intractable post- traumatic epilepsy. As such they are at risk for a number of complications including sudden death, physical injuries, memory loss and a host of psychosocial issues. Due to this problem, a call has been made by the American Epilepsy Society for chronic studies of post-traumatic epilepsy. Therefore, we have tailored our proposal to provide information for this need. In our preliminary studies, we have used a model of TBI called controlled cortical impact (CCI) in adult male rats and found that seizure threshold is not only decreased after CCI, but continues to decline for at least 6 months thereafter. At this time we propose to evaluate seizure threshold chronically after lateral CCI over the life-span of the adult rat, which is about 24 months. During that time, we plan to perform electrophysiological, histological and biochemical experiments in vitro and in vivo techniques to evaluate seizure threshold in hippocampal subregions, including the dentate, CA3 and CA1 every 6 months after CCI. We have also found in our preliminary studies, evidence that treatment with the Bcl-220-34 peptide may prevent the lowering of seizure threshold after CCI. Therefore, we will also evaluate this treatment strategy in our proposal. In addition, we will examine a potential mechanism of action for the Bcl-220-34 peptide, which may indicate mitochondrial involvement in the generation of lowered seizure threshold after TBI. To this end, we will also evaluate mitochondrial structure and function after CCI with and without treatment with the Bcl-220-34 peptide.

描述（由申请人提供）：