Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn, Bonn, Germany.
Unit of Epileptology and Experimental Neurophysiology, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy.
Epilepsia. 2017 Jul;58(7):1159-1171. doi: 10.1111/epi.13795. Epub 2017 May 24.
OBJECTIVE: Seizures in mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis are thought to develop with various latency intervals after an initial transient brain insult. To study seizure dynamics after an initial transient precipitating insult in a systematic fashion, we utilized continuous video-electroencephalography (EEG) monitoring after the induction of status epilepticus (SE) in a mouse MTLE model. METHODS: Continuous 24/7 video/telemetric hippocampal EEG recordings in the systemic pilocarpine MTLE mouse model. RESULTS: After SE, we observed emerging seizures interfering with the circadian EEG rhythms. The physiologic circadian EEG pattern of mice was transiently suppressed for 2.9 (mean) ± (SEM) 0.5 days after SE. This period was accompanied predominately by nonconvulsive seizure activity, followed by convulsive seizures at later stages. After the circadian rhythm was restored, spontaneous generalized seizures occurred mainly in a clustered manner in a narrow time window between 4 and 7 p.m. (light cycle 7 a.m./7 p.m.). Moreover, we demonstrate that depth-electrode implantation surgery transiently disturbs the physiologic EEG circadian cycle; variation of the time point of SE induction after electrode insertion surgery revealed a substantial impact on the epilepsy phenotype, which was more severe when SE occurred after postsurgical reappearance of EEG circadian cycling. SIGNIFICANCE: These data have several experimental and pathophysiologic implications. The impact of depth-electrode surgery on the phenotype has to be tightly controlled. In mice monitored after pilocarpine-induced SE, the "epileptogenesis" period is characterized by the dynamics of epileptiform activity toward behavioral recurrent seizure patterns. The striking clustering of spontaneous seizures at the transition from sleep to activity stages of mice has to be taken into account for future studies on the model. Improving our understanding of the molecular mechanisms that determine the circadian dynamics of seizure threshold remains an intriguing task for the future.
目的:人们认为,与海马硬化相关的内侧颞叶癫痫(MTLE)的发作,在初始短暂脑损伤后会有不同的潜伏期发展。为了系统地研究初始短暂诱发损伤后的癫痫发作动态,我们在 MTLE 小鼠模型中诱导癫痫持续状态(SE)后,利用连续视频-脑电图(EEG)监测。
方法:在全身性匹鲁卡品 MTLE 小鼠模型中进行 24/7 小时的连续视频/遥测海马 EEG 记录。
结果:在 SE 后,我们观察到出现的癫痫发作干扰了昼夜 EEG 节律。SE 后,小鼠的生理昼夜 EEG 模式暂时被抑制了 2.9(平均值)±(SEM)0.5 天。在此期间,主要以非惊厥性发作活动为特征,随后在后期出现惊厥性发作。在昼夜节律恢复后,自发性全身性发作主要以簇状方式发生在 4 点至 7 点之间的狭窄时间窗口(光照周期为 7 点/7 点)。此外,我们证明深部电极植入手术会短暂干扰生理 EEG 昼夜周期;在电极插入手术后,改变 SE 诱导的时间点会对癫痫表型产生实质性影响,当 SE 发生在 EEG 昼夜节律循环术后再次出现后更为严重。
意义:这些数据具有一些实验和病理生理学意义。深部电极手术对表型的影响必须得到严格控制。在接受匹鲁卡品诱导 SE 后监测的小鼠中,“癫痫发生”期的特征是癫痫样活动向行为性复发性发作模式的动态变化。在从睡眠到活动阶段过渡时,自发性癫痫发作的明显聚类,这是该模型未来研究中需要考虑的问题。提高我们对决定癫痫发作阈值昼夜动态的分子机制的理解仍然是未来一项有趣的任务。
Heliyon. 2024-11-14
Clocks Sleep. 2024-10-21
Front Neurol. 2023-5-18
Front Behav Neurosci. 2022-12-23