Data_Sheet_1_Conduction treatment of temporal lobe epilepsy in rats: the dose-effect relationship between current resistance and therapeutic effect.PDF

ObjectiveTo investigate the effect of current resistance on therapeutic outcomes, and the mechanism of current conduction treatment in a rat model of temporal lobe epilepsy (TLE).
MethodsRats were randomly divided into four groups: normal control, epileptic group, low-resistance conduction (LRC) and high-resistance conduction (HRC) group. The content of glutamate (Glu) and gamma-amino butyric acid (GABA) in the hippocampus was determined using a neurotransmitter analyzer. mRNA and protein expression of interleukin 1β (IL-1β) /IL-1 receptor 1(IL-1R1) and high mobility group protein B1 (HMGB-1)/toll-like receptor-4 (TLR-4) in hippocampal neurons were tested. Video electroencephalogram monitoring was used to record seizures and EEG discharges. Cognitive function in the rats was tested using the Morris water maze.
ResultsGlu/GABA ratio in the epileptic control and HRC groups was significant differences from LRC group. The levels of HMGB1/TLR4 and IL-1β/IL-1R1 in the LRC group and normal control group were significantly lower than those in epileptic control group (p < 0.01) and the HRC group. The mRNA levels of HMGB1/TLR4 and IL-1β/IL-1R1 in the LRC group and normal control group were significantly lower than those in epileptic control group. The frequency of total and propagated seizures was lower in the LRC group than in the epileptic control and HRC groups (p < 0.01). The numbers of platform crossings in the LRC group and normal control group were significantly higher than those in the epileptic control and HRC groups in the space exploration experiment.
ConclusionCurrent resistance affected seizure control and cognitive protection in rats with TLE treated by current conduction. The lower current resistance, the better seizure control and cognitive protection in rats with TLE treated by current conduction. Glu/GABA, IL-1β/IL-1R1, and HMGB1/TLR-4 may participate in the anti-seizure mechanism of current conduction treatment.

研究目的：探究电流阻抗对颞叶癫痫（Temporal Lobe Epilepsy, TLE）大鼠模型的治疗结局的影响，以及电流传导治疗的作用机制。
方法：将大鼠随机分为四组：正常对照组、癫痫模型组、低阻抗传导（Low-resistance Conduction, LRC）组与高阻抗传导（High-resistance Conduction, HRC）组。采用神经递质分析仪检测海马组织中谷氨酸（Glutamate, Glu）与γ-氨基丁酸（Gamma-Aminobutyric Acid, GABA）的含量；检测海马神经元中白细胞介素1β（Interleukin 1β, IL-1β）/IL-1受体1（IL-1 Receptor 1, IL-1R1）及高迁移率族蛋白B1（High Mobility Group Protein B1, HMGB-1)/Toll样受体4（Toll-like Receptor-4, TLR-4）的mRNA与蛋白表达水平；采用视频脑电图监测记录癫痫发作及脑电图放电情况；采用Morris水迷宫实验检测大鼠认知功能。
结果：癫痫模型组与高阻抗传导组的Glu/GABA比值与低阻抗传导组相比存在显著差异。低阻抗传导组与正常对照组的HMGB1/TLR4及IL-1β/IL-1R1蛋白水平均显著低于癫痫模型组与高阻抗传导组（p<0.01）；两组的HMGB1/TLR4及IL-1β/IL-1R1 mRNA水平亦显著低于癫痫模型组。低阻抗传导组的全面性发作与传导性发作频率均显著低于癫痫模型组与高阻抗传导组（p<0.01）。空间探索实验中，低阻抗传导组与正常对照组的平台穿越次数均显著高于癫痫模型组与高阻抗传导组。
结论：电流阻抗可影响接受电流传导治疗的颞叶癫痫大鼠的癫痫控制效果与认知保护作用。接受电流传导治疗的颞叶癫痫大鼠，电流阻抗越低，其癫痫控制效果与认知保护作用越好。Glu/GABA、IL-1β/IL-1R1及HMGB1/TLR-4或参与电流传导治疗的抗癫痫机制。