Chronobiology of partial epilepsy

描述（由申请人提供）：内侧颞叶癫痫（MTLE）， 最常见的部分性癫痫，占大多数患者， 无法控制的癫痫MTLE中的癫痫发作不是随机发生的， 日常模式对癫痫发作时间的可能影响包括 昼夜节律振荡的基础因素，促进或抑制 癫痫发作下丘脑-垂体-肾上腺轴（HPAA）的影响 是调节癫痫发作的合理候选者，将成为 提出的实验。本提案审查了 在一个独特的部分性癫痫动物模型中， 与具有临床、电图、组织学和时间相似性 MTLE。本建议的具体目的是评估内生性的作用， HPAA在实验性边缘系统昼夜节律调节中的节律性 癫痫 假设1. HPAA的节律性在实验性癫痫中是完整的。 假设2.皮质酮释放激素（CRH）受到不同程度的影响， 在下丘脑和边缘系统的病变，在不同水平的 clockHPAA系统。我们的数据表明，昼夜节律机制继续 在癫痫大鼠的功能和神经元密度的重要区域， HPAA调节正常。我们将评估CRH表达是否仍然存在， 在完整的动物以及有生物钟损伤的动物中， 或HPAA。 假设3. CRH和皮质酮的正常变化是必要的， 边缘癫痫的昼夜节律复发我们预测， 将导致癫痫发作的昼夜分布发生变化。 先前的研究结果表明，癫痫发作发生在一个内源性介导的昼夜节律 节奏..总之，这些研究将提供深入了解 促进部分癫痫发作表达的时间因素， 为治疗控制不良的部分 癫痫

DESCRIPTION (provided by applicant): Mesial temporal lobe epilepsy (MTLE), the most common partial epilepsy, accounts for the majority of patients with uncontrolled seizures. Seizures in MTLE do not strike randomly but occur in daily patterns. Possible influences on the timing of seizures include those factors that underlie circadian oscillation and that facilitate or inhibit seizures. Influences provided by the hypothalamicpituitaryadrenal axis (HPAA) are logical candidates to modulate seizures and will be the focus of the proposed experiments. This proposal examines the temporal distribution of spontaneous, limbic seizures in a unique animal model of partial epileps~ that shares clinical, electrographic, histological, and timing similarities with MTLE. The specific aim of this proposal is to evaluate the role of endogenous rhythmicity of the HPAA in the circadian modulation of experimental limbic epilepsy. Hypothesis 1. Rhythmicity of the HPAA is intact in experimental epilepsy. Hypothesis 2. Corticosterone releasing hormone (CRH) is differentially affected within the hypothalamus and limbic system by lesions at different levels of the clockHPAA system. Our data suggests that circadian mechanisms continue to function in the epileptic rat and that neuronal density in regions important in HPAA regulation is normal. We will evaluate whether CRH expression remains rhythmic in intact animals as well as in animals that have lesions of the clock or of the HPAA. Hypothesis 3. The normal variations of CRH and corticosterone are necessary for circadian recurrence of limbic seizures. We predict that alterations of inputs into the HPAA will cause changes in the circadian distribution of seizures. Previous results show that seizures occur in an endogenously mediated circadian rhythm.. In summary, these studies will provide insight into the chronoblological factors that facilitate partial seizure expression and may provide new perspectives into treatments for poorly controlled partial epilepsy.