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左侧丘脑前核电刺激,采用高频、低强度电流,可降低匹罗卡品致痫大鼠的癫痫发作频率。

Electrical stimulation of left anterior thalamic nucleus with high-frequency and low-intensity currents reduces the rate of pilocarpine-induced epilepsy in rats.

机构信息

Department of Neurology, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan, ROC.

出版信息

Seizure. 2013 Apr;22(3):221-9. doi: 10.1016/j.seizure.2012.12.015. Epub 2013 Jan 11.

DOI:10.1016/j.seizure.2012.12.015
PMID:23313409
Abstract

PURPOSE

Bilateral electrical stimulation of anterior nuclei of thalamus (ANT) has shown promising effects on epileptic seizures. However, bilateral implantation increases the risk of surgical complications and side effects. This study was undertaken to access the effectiveness of a stimulation paradigm involving high frequency and low intensity currents to stimulate the left ANT in rats.

METHODS

Male Sprague-Dawley rats were implanted with electroencephalogram (EEG) electrodes, and an additional concentric bipolar stimulation electrode into either the left or right ANT. The stimulus was a train of pulses (90 μs duration each) delivered with a frequency of 200 Hz and a current intensity of 50 μA. Thalamic stimuli were started 1 h before the first intraperitoneal pilocarpine injection (i.p., 300 mg/kg), and were applied for 5 h.

RESULTS

EEG documented seizure activity and status epilepticus (SE) developed in 87.5% of rats treated with no ANT stimulation after a single dose of pilocarpine. Left ANT stimulation significantly increased the tolerance threshold for pilocarpine-induced EEG seizure activity; 20% of rats developed their EEG documented seizure activity after receiving the first dose, whereas 50%, 10% and 20% of rats did not develop seizure activity until they had received the 2nd, 3rd and 4th pilocarpine injection at 1-h intervals. Moreover, left thalamic stimulation reduced the occurrences of both EEG documented seizure activity and SE induced by single-dose pilocarpine to 25%. However, our result demonstrated that little effect on the occurrence rate of seizures and SE was found when rats received right ANT stimulation.

CONCLUSIONS

These results suggest that continuously 5-h left ANT stimulation with high frequency and low intensity currents, beginning from 1h before the pilocarpine administration, may successfully reduce the occurrence rate of EEG documented seizure activity and SE development in rats.

摘要

目的

双侧丘脑前核(ANT)电刺激对癫痫发作有明显的治疗效果。但是,双侧植入增加了手术并发症和副作用的风险。本研究旨在评估一种刺激范式的有效性,该范式涉及高频和低强度电流刺激大鼠左侧 ANT。

方法

雄性 Sprague-Dawley 大鼠植入脑电图(EEG)电极,并在左侧或右侧 ANT 中植入另外一个同心双极刺激电极。刺激是一个脉冲串(每个脉冲持续 90μs),频率为 200Hz,电流强度为 50μA。丘脑刺激在首次腹腔注射毛果芸香碱(i.p.,300mg/kg)前 1 小时开始,并持续 5 小时。

结果

脑电图记录到癫痫发作活动和癫痫持续状态(SE)在没有 ANT 刺激的情况下,87.5%的大鼠在单次毛果芸香碱处理后出现。左侧 ANT 刺激显著增加了毛果芸香碱诱导的 EEG 癫痫发作活动的耐受阈值;20%的大鼠在接受第一剂药物后出现脑电图记录的癫痫发作活动,而 50%、10%和 20%的大鼠直到接受 1 小时间隔的第 2、3 和 4 次毛果芸香碱注射后才出现癫痫发作活动。此外,左侧丘脑刺激将单次毛果芸香碱诱导的 EEG 记录的癫痫发作活动和 SE 的发生率降低至 25%。然而,我们的结果表明,右侧 ANT 刺激对单次毛果芸香碱诱导的癫痫发作和 SE 的发生率几乎没有影响。

结论

这些结果表明,从毛果芸香碱给药前 1 小时开始,连续 5 小时用高频和低强度电流刺激左侧 ANT,可能成功降低大鼠 EEG 记录的癫痫发作活动和 SE 发展的发生率。

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