Post Traumatic Nonconvulsive Epileptiform Activity

创伤后非惊厥性癫痫样活动

• 批准号: 6529067
• 负责人: Paul M Vespa
• 金额: $ 10.76万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-06 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6529067
• 关键词: brain cell; brain injury; cell membrane; cerebral ischemia /hypoxia; clinical research; coma; electroencephalography; epilepsy; gamma aminobutyrate; glucose metabolism; glycerol; glycolysis; human subject; hyperglycemia; magnesium; microdialysis; neurochemistry; neurons; phospholipids; posttraumatic stress disorder

DESCRIPTION (provided by applicant): The main aim of this proposal is to study the incidence of epileptiform discharges and seizures that occur during coma after traumatic brain injury, possible mechanisms of generating epileptiform activity and the neurochemical consequences of this activity. The investigator has made exciting preliminary observations that post-traumatic nonconvulsive seizure activity on continuous electroencephalography (EEG) occurs frequently, is associated with adverse neurochernical changes and increases mortality. Previous animal brain injury models have documented neurochernical and ionic perturbation with an energy crisis and compensatory hyperglycolysis. At the same time there is a selective loss of neuronal inhibition (GABA, y-amino-butyric acid, containing cells) and reduced extracellular magnesium that leads to a decrease in seizure threshold. As a consequence of early post traumatic seizures, cellular energy demand may be increased and lead to secondary injury of cells that survived the initial trauma. Preliminary studies demonstrate an increased incidence of EEG-defined seizures. and epileptiforin activity, however the relationship between early post-traumatic epileptiform activity, the disordered neurochernical state, increased glucose metabolism and secondary cellular injury remain unknown. Thus the central hypothesis of this grant is that early post-traumatic nonconvulsive epileptiform activity is common and leads to further hyperglycolytic neurochernical events (increased lactate, glutamate and decreased glucose) and additional neuronal membrane injury. The specific aims of this proposal will be: (1) delineate the incidence rate, type and duration of early EEG-defined post-traumatic epileptiform activity (TEEA); (2) define the mechanistic influence of impaired neuronal inhibition in generating TEEA; (3) determine if TEEA results in a hyperglycolytic response; and (4) determine if TEEA leads to additional brain tissue membrane injury, as determined by time-locked increases in extracellular glycerol. The application is intended to pen-nit the candidate to gain important didactic education in research and statistical methods and experience in conducting a human-based basic research paradigm complemented by future animal models. The hypothesis and unique approach come at a crucial time of failed clinical trials and address an important new therapeutic target.

描述(申请人提供)：本提案的主要目的是研究 昏迷期间癫痫样放电和癫痫发作的发生率 创伤性脑损伤后癫痫样形成的可能机制 活动和这种活动的神经化学后果。调查员 已经做出了令人兴奋的初步观察，创伤后的非抽搐 连续脑电(EEG)上的癫痫活动频繁发生， 与不利的神经神经改变相关，并增加死亡率。 以前的动物脑损伤模型记录了神经性和离子性脑损伤 能量危机和代偿性高糖酵解的不安。在 同时有选择性的神经元抑制丧失(GABA， 含细胞的Y-氨基丁酸)和还原的胞外镁 这会导致癫痫发作阈值的降低。由于提早发帖 创伤性癫痫发作，细胞能量需求可能增加并导致 在最初的创伤中幸存下来的细胞的二次损伤。初步研究 显示脑电波定义的癫痫的发生率增加。和癫痫福林 然而，活动与创伤后早期癫痫样改变之间的关系 活动，无序的神经精神状态，葡萄糖代谢增加和 继发性细胞损伤仍不清楚。因此，这一观点的中心假设 格兰特认为，早期创伤后非惊厥性癫痫样活动是 常见，并导致进一步的高糖酵解神经性事件(增加 乳酸、谷氨酸和降糖)和额外的神经细胞膜 受伤。这项建议的具体目标将是：(1)划定事件 早期脑电确定的创伤后癫痫样改变的发生率、类型和持续时间 活动(TEEA)；(2)定义受损神经元的机械影响 抑制TEEA的产生；(3)确定TEEA是否导致 高糖酵解反应；以及(4)确定TeEA是否会导致额外的大脑 由细胞外时间锁定增加所确定的组织膜损伤 甘油。这份申请书的用意是让应聘者获得 在研究和统计方法和经验方面的重要教学教育 在开展以人为本的基础研究范式方面 并辅之以未来的动物模型。假设和独特的方法来了 在临床试验失败的关键时刻，并解决一个重要的新 治疗靶点。