Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats

Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats
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DOI:
10.1111/j.1528-1167.2005.00268.x
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发表时间:
2005-10-01
期刊:
影响因子:
5.6
通讯作者:
Engel, J
Engel, J
中科院分区:
医学1区
文献类型:
--
作者:
Bragin, A;Azizyan, A;Engel, J

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目的:本研究的目的是分析单侧海马内注射红藻氨酸(KA)后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。方法:麻醉下在海马前后齿状回(DG)和CA1区以及内嗅皮质的对称点双侧植入一对钨电极(50μm O/D)。成年 Wistar 大鼠。基线脑电图记录 1 周后,将刺激电极放置在右角束中,并将 KA 注射到海马右后 CA3 区域。注射后 24 小时开始,每天用视频监测癫痫发作记录电图活动,持续 8 小时/天,持续 60 天。结果:70% 的癫痫发作在注射同侧 DG 局部开始,伴随发作间期 EEG 尖峰频率增加(超同步型,HYP),26% 的癫痫发作开始时 EEG 振幅降低,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-gamma 范围频率、纹波频率和快速纹波 (FR) 频率的幅度显着增加,而在 LVF 癫痫发作期间,仅在 β-gamma 范围内观察到增加。除一种情况外,在所有情况下,EEG 波都先于纹波和 FR 振荡。在癫痫发作之前,DG 诱发的对单个脉冲的反应幅度减小,而对以 30 ms 间隔传递的第二个脉冲的反应幅度增加。结论:如果纹波和 FR 振荡表明癫痫发作的神经元基质,这些区域一定很小且广泛,因此直接从它们记录的概率非常低。癫痫发作前对电刺激的反应减弱可能表明存在抑制或预防癫痫发作的保护性抑制机制。成对脉冲抑制的减少可能表明网络倾向于遵循特定频率的外部输入。
Purpose: 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.Methods: Pairs of tungsten electrodes (50 mu m 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.Results: 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.Conclusions: 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.