Progression of temporal lobe epilepsy

超出所提供的空间。尽管流行病学研究为颞叶癫痫提供了有价值的视角，但人类研究的伦理限制阻碍了对一个重要问题的明确回答：抗癫痫药物（AED）治疗是纯粹的症状性治疗，还是影响癫痫的自然史？本实验采用颞叶癫痫动物模型来确定自发性癫痫发作是否会损害大脑并增加癫痫发作的可能性（即促进癫痫发生），反之，减少抗癫痫药的发作次数是否会显著减少脑损伤和癫痫发生。中心假设是，长期使用AED治疗可以显著减少自发性癫痫发作，导致停用AED后癫痫发作的频率和严重程度长期降低。kainate治疗的大鼠是一种特征良好的颞叶癫痫动物模型，将用于确定癫痫持续状态后几个月内自发发作频率的逐渐增加是否会继续损害海马并导致癫痫发生。AED（即苯妥英、苯巴比妥和丙戊酸盐）将用于长时间阻断自发性癫痫发作，以确定AED治疗是否减少癫痫发生并导致自发性癫痫发作频率的长期降低（即，在AED治疗停止后频率持续降低）。一个相关的假设是，延长AED治疗可减少神经元死亡和海马癫痫发生的其他潜在标志物。电图癫痫发作的慢性记录、定量组织病理学研究以及海马切片中突触和癫痫样事件的体外电生理记录将被用来确定长期AED治疗是否会减少神经元损伤、神经回路重组和癫痫发生。这些实验将提供关于癫痫发作频率对脑损伤和未来癫痫发作倾向的影响的精确和有价值的信息，这将对了解癫痫发生机制以及对AED治疗和癫痫手术做出临床决策具有重要意义。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Although epidemiological studies have provided valuable perspectives on temporal lobe epilepsy, the ethical limitations of human research prevent a definitive answer to the important question: is antiepileptic drug (AED) therapy purely symptomatic, or does it affect the natural history of the epilepsy? The proposed experiments use an animal model of temporal lobe epilepsy to determine whether spontaneous epileptic seizures damage the brain and increase the likelihood of more seizures (i.e., promote epileptogenesis), and conversely, whether decreasing the number of seizures with AEDs significantly reduces brain damage and epileptogenesis. The central hypothesis is that prolonged treatment with an AED, which significantly reduces spontaneous epileptic seizures, causes long-term reductions in the frequency and severity of subsequent epileptic seizures after AED withdrawal. The kainate-treated rat, a well-characterized animal model of temporal lobe epilepsy, will be used to determine whether the progressive increase in the frequency of spontaneous seizures during the months after status epilepticus continues to damage the hippocampus and contributes to epileptogenesis. AEDs (i.e., phenytoin, phenobarbital, and valproate) will be used to block spontaneous epileptic seizures for prolonged periods to determine whether AED therapy reduces epileptogenesis and results in a long-term decrease in spontaneous seizure frequency (i.e., a decrease in frequency that persists after the AED therapy has been withdrawn). A related hypothesis is that prolonged AED treatment reduces neuronal death and other potential markers of hippocampal epileptogenesis. Chronic recording of electrographic seizures, quantitative histopathological studies, and in vitro electrophysiological recording of synaptic and epileptiform events in hippocampal slices will be used to determine if prolonged AED treatment decreases neuronal damage, reorganization of neural circuits, and epileptogenesis. These experiments will provide precise and valuable information regarding the influence of seizure frequency on brain damage and on the propensity for future seizures, which will be important for understanding the mechanisms of epileptogenesis and for making clinical decisions regarding AED therapy and epilepsy surgery. PERFORMANCE SITE ========================================Section End===========================================