闭环式电刺激抑制痫样棘波发放的机制研究  

Mechanism of Suppression of Epileptiform Burst by Closed-Loop Electrical Stimulation

作　　者：曹嘉悦 封洲燕[1] 郭哲杉 胡振华[1] 胡娜[1] 

机构地区：[1]浙江大学生物医学工程与仪器科学学院生物医学工程教育部重点实验室,杭州310027

出　　处：《中国生物医学工程学报》2016年第1期79-87,共9页Chinese Journal of Biomedical Engineering

基　　金：国家重点基础研究发展计划(973计划)(2011CB504400)

摘　　要：脑深部刺激（DBS）在临床癫痫病的治疗中备受关注,可能替代癫痫病灶的切除手术。但是,癫痫的发作机制多种多样,需要针对性地设计DBS的刺激模式和参数,才能获得较好的疗效。对于γ-氨基丁酸受体的拮抗剂印防己毒素在麻醉大鼠海马CA1区诱导的痫样发放,采用短促的高频刺激（HFS）脉冲串;并利用闭环式的刺激模式,在各个爆发式发放期间,将脉冲串施加于CA1区的传入轴突束Schaffer侧支。9只大鼠的实验结果表明,100 Hz以上的0.3 s时长HFS可以抑制Burst中60%~70%的棘波发放。而且,在HFS抑制棘波发放期间,CA1区神经元不能响应其传出轴突束上施加的逆向刺激脉冲的激励作用,表明在此期间神经元失去了产生动作电位的能力。由此可以推测,HFS抑制棘波发放的机制可能是神经元细胞膜发生了去极化阻滞。该研究的发现对于开发DBS治疗癫痫的闭环刺激新模式具有重要的指导意义。Deep brain stimulation （DBS） is an attractive alternative strategy to surgical excision of the seizure focuses for epilepsy treatments in clinic. However, epilepsy can be generated by various mechanisms, and this highlights a need in designing pertinent DBS patterns with customized parameters for the effective therapy. In the present study, high-frequency stimulation （HFS） pulse trains with short durations were used against the epileptic form activity induced by picrotoxin, an antagonist of GABAergic receptors, in the hippocampal CA1 region of anaesthetized rats. In a closed-loop manner, the HFS train was applied during each period of epileptic form bursts to the afferent axon tracts （i. e. the Schaffer collaterals） of CA1 region. The experiment results from 9 rats show that HFS trains with a frequency over 100 Hz and duration of 0.3 s during bursts suppressed 60 -70% of the spikes in the bursts. Meanwhile, during the periods of HFS against bursts, the neurons of CA1 region failed to respond to the excitation of antidromic stimulation applied to the efferent axon tracts （i. e. the alveus）, indicating that the neurons temporarily lost their ability to generate action potentials. Therefore, presumably, the mechanism of spike suppression by HFS might be a depolarization block generated within neuronal membranes. The finding of the study provides important insight into the development of novel closed- loop stimulation patterns of DBS in treating epilepsy.

关 键 词：脑深部刺激 闭环 癫痫 印防己毒素 去极化阻滞 

分 类 号：R338[医药卫生—人体生理学] R318[医药卫生—基础医学]