Chronobiology of partial epilepsy

描述(申请人提供)：内侧颞叶癫痫(MTLE)， 最常见的部分性癫痫，占大多数患者的 失控的癫痫发作。MTLE的癫痫发作不是随机发作的，而是发生在 日常生活模式。对癫痫发作时间的可能影响包括 昼夜节律振荡的基础和促进或抑制的因素 癫痫发作。下丘脑-垂体-肾上腺轴(HPAA)的影响 是调制癫痫发作的合乎逻辑的候选者，并将成为 拟议的实验。这项建议研究了 一种独特的部分性癫痫动物模型中的自发性边缘癫痫发作 在临床、脑电、组织学和时间上与 MTLE。这项建议的具体目的是评估内源性的作用 HPAA在实验性边缘昼夜节律调节中的节律性 癫痫。 假设1.实验性癫痫患者HPAA的节律性是完整的。 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内由不同水平的病变 时钟HPAA系统。我们的数据表明，昼夜节律机制继续 癫痫大鼠的功能和脑内重要区域的神经元密度 HPAA调节正常。我们将评估CRH的表达是否保持 在完整的动物和有时钟损伤的动物中都是有节律性的 或者是HPAA的。 假设3：CRH和皮质酮的正常变化对 边缘发作的昼夜节律复发。我们预测，投入的变化 进入HPAA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内源性的昼夜节律中。 节奏..。总而言之，这些研究将为我们提供对 促进部分癫痫发作表达的时序因素，并可能 为控制不佳的部分性皮炎的治疗提供新的视角 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.