Department of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Epilepsia. 2012 Jan;53(1):147-56. doi: 10.1111/j.1528-1167.2011.03348.x. Epub 2011 Dec 9.
To investigate the effects of low frequency stimulation (LFS) of a fiber tract for the suppression of spontaneous seizures in a rat model of human temporal lobe epilepsy.
Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recording electrodes were placed in the CA3 regions bilaterally and neural data were recorded for a minimum of 6 weeks. LFS (60 min train of 1 Hz biphasic square wave pulses, each 0.1 ms in duration and 200 μA in amplitude, followed by 15 min of rest) was applied to the VHC for 2 weeks, 24 h a day.
The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n = 7). By the end of the 2-week period of stimulation, there was a significant, 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during 2 weeks of LFS session. The hippocampal histologic analysis showed no significant difference between rats that received LFS and SE induction and those that had received only SE-induction. None of the animals showed any symptomatic hemorrhage, infection, or complication.
Low frequency stimulation applied at a frequency of 1 Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could lead to the development of a new therapeutic modality for human patients with temporal lobe epilepsy.
研究低频刺激纤维束对颞叶癫痫(TLE)大鼠模型自发性癫痫发作的抑制作用。
在颞叶癫痫(TLE)大鼠癫痫后(SE)模型中,将刺激电极植入腹侧海马连合(VHC)(n=7)。双侧 CA3 区放置两个记录电极,记录至少 6 周的神经数据。VHC 每天 24 小时进行 2 周的 LFS(60 分钟 1 Hz 双相方波脉冲,每个脉冲持续 0.1 毫秒,幅度为 200 μA)。
研究动物的基线平均癫痫发作频率为每天 3.7 次。在每只动物(n=7)中,LFS 的应用均显著减少了癫痫发作。在刺激的 2 周期间结束时,与基线相比,癫痫发作频率显著降低了 90%(<1 次/天)(p<0.05),在 LFS 之后的期间内降低了 57%(p<0.05)。LFS 还导致海马间发性尖峰频率显著降低(71%,p<0.05),在 2 周的 LFS 期间。海马组织学分析显示,接受 LFS 和 SE 诱导的大鼠与仅接受 SE 诱导的大鼠之间无显著差异。没有动物出现任何症状性出血、感染或并发症。
以 1 Hz 的频率施加的低频刺激显著降低了 TLE 大鼠模型中神经组织的兴奋性和癫痫发作频率。这些结果支持了纤维束 LFS 可以是抑制大鼠 TLE 模型中自发性癫痫发作的有效方法的假说,并可能导致开发一种新的治疗方法用于人类 TLE 患者。