Bragin Anatol, Azizyan Avetis, Almajano Joyel, Wilson Charles L, Engel Jerome
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Epilepsia. 2005 Oct;46(10):1592-8. doi: 10.1111/j.1528-1167.2005.00268.x.
The goal of this study was to analyze the transition period between interictal and ictal activity in freely moving rats with recurrent spontaneous seizures after unilateral intrahippocampal kainic acid (KA) injection.
Pairs of tungsten electrodes (50 microm O/D) were implanted bilaterally under anesthesia at symmetrical points in the dentate gyrus (DG) and CA1 regions of anterior and posterior hippocampi and entorhinal cortex of adult Wistar rats. Stimulating electrodes were placed in the right angular bundle and KA was injected into the right posterior CA3 area of hippocampus after 1 week of baseline EEG recording. Beginning 24 h after injection, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for 60 days.
Seventy percent of seizures started locally in the DG ipsilateral to injection, with an increase in frequency of interictal EEG spikes (hypersynchronous type, HYP), and 26% of seizures started with a decrease of EEG amplitude with parallel increase in frequency (low-voltage fast type, LVF). During HYP seizures, a significant increase was observed in amplitude of beta-gamma range frequencies, ripple frequency, and fast ripple (FR) frequency, whereas during LVF seizure, an increase was noted only in the beta-gamma range. In all cases but one, an EEG wave preceded ripple and FR oscillations. Before seizure onset, the amplitude of DG-evoked responses to single pulses decreased, whereas the amplitude of the response to the second pulse delivered at 30-ms interval increased.
If ripple and FR oscillations indicate the seizure-generating neuronal substrate, these areas must be small and widespread, so that the probability of recording from them directly is very low. The decreased response to electrical stimulation before seizures could indicate a protective inhibitory mechanism that contains or prevents seizure occurrence. The presence of decreased paired-pulse suppression could indicate a network predisposition to follow an external input with a certain frequency.
本研究的目的是分析单侧海马内注射 kainic 酸（KA）后出现反复自发性癫痫发作的自由活动大鼠发作间期和发作期活动之间的过渡期。
在成年 Wistar 大鼠的前、后海马齿状回（DG）和 CA1 区域以及内嗅皮质的对称点，于麻醉状态下双侧植入成对的钨电极（外径 50 微米）。刺激电极置于右侧角束，在基线脑电图记录 1 周后，将 KA 注入右侧海马后 CA3 区。注射后 24 小时开始，每天进行 8 小时的视频监测脑电图活动，持续 60 天以记录癫痫发作情况。
70%的癫痫发作起始于注射侧同侧的 DG 局部区域，发作间期脑电图尖波（超同步型，HYP）频率增加，26%的癫痫发作起始于脑电图幅度降低且频率平行增加（低电压快速型，LVF）。在 HYP 癫痫发作期间，观察到β-γ频段频率、涟漪频率和快速涟漪（FR）频率的幅度显著增加，而在 LVF 癫痫发作期间，仅β-γ频段有增加。除一例之外，在所有情况下，脑电图波先于涟漪和 FR 振荡出现。在癫痫发作开始前，DG 对单个脉冲诱发反应的幅度降低，而以 30 毫秒间隔施加的第二个脉冲的反应幅度增加。
如果涟漪和 FR 振荡表明癫痫发作产生的神经元基质，那么这些区域必定小且分布广泛，因此直接记录到它们的概率非常低。癫痫发作前对电刺激反应的降低可能表明存在一种抑制癫痫发作发生的保护性抑制机制。成对脉冲抑制降低的存在可能表明网络倾向于以特定频率跟随外部输入。
