Post Traumatic Nonconvulsive Epileptiform Activity

描述（由申请人提供）：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发作的可能机制 活动和这种活动的神经化学后果。研究者 做了令人兴奋的初步观察， 连续脑电图（EEG）上的癫痫活动频繁发生， 与不利的神经化学变化和增加死亡率有关。 以前的动物脑损伤模型已经记录了神经化学和离子 能量危机和代偿性高糖酵解的扰动。在 同时存在神经元抑制的选择性丧失（GABA， γ-氨基丁酸，含有细胞）和减少的细胞外镁 导致癫痫发作阈值降低由于早期的职位 创伤性癫痫发作，细胞能量需求可能增加，并导致 在最初创伤中存活下来的细胞的继发性损伤。初步研究 表明EEG定义的癫痫发作的发生率增加。和癫痫素 活动，然而，早期创伤后癫痫样 活动，神经化学状态紊乱，葡萄糖代谢增加， 继发性细胞损伤仍不清楚。因此，这个问题的核心假设 早期创伤后非惊厥性癫痫样活动 常见，并导致进一步的高糖酵解神经化学事件（增加 乳酸盐、谷氨酸盐和葡萄糖减少）和额外的神经元膜 损伤这项建议的具体目标是：（1）界定发病率 早期EEG定义的创伤后癫痫样发作的发生率、类型和持续时间 活动（TEEA）;（2）定义受损神经元的机械影响 抑制产生TEEA;（3）确定TEEA是否导致 高糖酵解反应;和（4）确定TEEA是否导致额外的脑 组织膜损伤，通过细胞外时间锁定增加确定 甘油申请书的目的是让候选人获得 在研究和统计方法和经验方面的重要教学教育 以人为本的基础研究范式 未来的动物模型。假设和独特的方法来 在临床试验失败的关键时刻， 治疗靶点

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.