Bayat Arezou, Skopin Mark D, Joshi Sweta, Siddu Mithilesh, Mukharesh Loulwah, Jahan Sahar, Tsuchiya Komei, Connell Phillip, Younes Naji, Koubeissi Mohamad Z
Department of Neurology, George Washington University, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA.
Milken Institute School of Public Health, George Washington University, 950 New Hampshire Ave. NW, Washington, DC 20052, USA.
Epilepsy Behav. 2017 Jul;72:1-7. doi: 10.1016/j.yebeh.2017.04.002. Epub 2017 May 28.
Recent evidence in animals and humans suggests that low-frequency stimulation (LFS) has significant antiepileptic properties. The anterior piriform cortex (APC) is a highly susceptible seizure-trigger zone and may be critical for the initiation and propagation of seizures originating from cortical and limbic foci. We used the kainic acid (KA) seizure model in rats to assess the therapeutic effect of LFS of the APC on seizures.
Adult male Sprague-Dawley rats were implanted with electrodes in the left APC and recording electrodes bilaterally in the hippocampal CA3 regions. Rats were monitored continuously with video-EEG after the emergence of spontaneous recurrent seizures that followed induction of status epilepticus by intraperitoneal KA. After two weeks of baseline recordings to determine seizure frequency, LFS of the APC was applied 60-min On 15-min Off, for two weeks with 1Hz biphasic square waves, 0.2ms pulse width, at 200μA. Another 2-week period of video-EEG monitoring was done after the cessation of LFS to study the carry-over effect. Changes in seizure frequency, severity, and duration between baseline, during LFS, and post-LFS were analyzed using the Poisson regression model.
Overall seizure frequency decreased during the post-LFS period to 5% of that at baseline (p=0.003). Severe seizures (stages 4 and 5 on the Racine scale) decreased to 0% of the baseline during the post-LFS period.
Two weeks of LFS of the APC reduced spontaneous seizure frequency and severity in the KA model with the effect outlasting the stimulation. Our findings suggest that the APC can be an important therapeutic target for stimulation in epilepsy.
动物和人类的最新证据表明，低频刺激（LFS）具有显著的抗癫痫特性。前梨状皮质（APC）是一个高度易引发癫痫的区域，对于源自皮质和边缘系统病灶的癫痫发作的起始和传播可能至关重要。我们使用大鼠的 kainic 酸（KA）癫痫模型来评估 APC 的 LFS 对癫痫发作的治疗效果。
成年雄性 Sprague-Dawley 大鼠在左侧 APC 植入电极，并在双侧海马 CA3 区域植入记录电极。通过腹腔注射 KA 诱导癫痫持续状态后，在出现自发性反复癫痫发作后，用视频脑电图连续监测大鼠。在进行两周的基线记录以确定癫痫发作频率后，以 1Hz 的双相方波、0.2ms 的脉冲宽度、200μA 的电流，对 APC 进行 60 分钟开启、15 分钟关闭的 LFS，持续两周。在 LFS 停止后，再进行两周的视频脑电图监测，以研究延续效应。使用泊松回归模型分析基线、LFS 期间和 LFS 后癫痫发作频率、严重程度和持续时间的变化。
LFS 后总体癫痫发作频率降至基线时的 5%（p = 0.003）。严重癫痫发作（Racine 分级的 4 级和 5 级）在 LFS 后降至基线时的 0%。
在 KA 模型中，对 APC 进行两周的 LFS 可降低自发性癫痫发作频率和严重程度，且该效果在刺激停止后仍持续存在。我们的研究结果表明，APC 可能是癫痫刺激治疗的一个重要靶点。
