高频电刺激丘脑背内侧核团对大鼠急性戊四唑癫痫模型的作用

Highfrequency stimulation of mediodorsal thalamic nucleus inhibits pentylenetetrazole-induced seizures in rats

目的 深部脑刺激(Deep brain stimulation,DBS)是治疗难治性癫痫的一种方式,以往的研究显示丘脑背内侧核团(Mediodorsal thalamic nucleus,MD)与癫痫发作相关,研究旨在探讨高频电刺激MD对急性戊四唑(Pentylenetetrazol,PTZ)癫痫模型中大鼠癫痫发作的影响.方法 实验选用由浙江医学科学院动物实验中心提供的成年健康雄性SD大鼠(280 ~350 g),根据不同刺激分为假刺激单双侧MD组、100 Hz高频电刺激(High frequency stimulation,HFS)刺激单侧MD组和双侧MD组,1Hz低频电刺激(Low frequency stimulation,LFS)刺激单侧MD组,共41只.用视频脑电装置同步记录各组PTZ急性致痫大鼠的行为和皮层脑电图,根据改良Racine分级系统评定癫痫发作等级.结果 LFS刺激单侧和HFS刺激单侧或双侧MD都不改变3级和5级发作的首个棘波或脑电图表现的潜伏期;HFS刺激单侧或双侧MD在减少阵挛性发作次数的同时能同步减少相应脑电图上的痫样放电次数;LFS刺激单侧MD在不改变阵挛性发作次数的同时也不改变相应脑电图上痫样放电波形及放电次数.相比于对照组(单侧或双侧假刺激组),HFS刺激单侧或双义侧MD能显著降低急性PTZ癫痫模型中大鼠发作的等级、缩短阵挛性发作(4~5级发作)的持续时间、减少相应发作的次数,但不改变肌阵挛性发作的潜伏期,而LFS刺激单侧MD对发作并无明显作用.结论 HFS刺激单侧或双侧MD可能是治疗全面性癫痫发作的一种潜在方法,临床中DBS的应用需要充分考虑癫痫发作的类型.

Objective The optimal target of deep brain stimulation(DBS)for treating intractable epilepsy is still undefined.Cumulative studies suggest that the mediodorsal thalamic nucleus(MD)is involved in seizure activity,the purpose of this study was to investigate the efect of high frequency stimulation in MD on pentylenetetrazole(PTZ)induced seizures in rats.Methods The experimental rats(Male Sprague-Dawley rats 280-350 g)were all provided by Experimental Animal Center,Zhejiang Academy of Medical Science,Hangzhou,China.The rats were given unilateral or bilateral stimulation of the MD at 100 Hz(HFS group)and sham stimulation,others were given unilateral stimulation of the MD at 1 Hz(LFS group).EECs in the cortex and seizure behavior were recorded with the Neuroscan system at the same time.Results Neither LFS nor HFS of the MD changed the latency to the first spikes or EEG manifestations for stage 3 and stage 5 seizures;animals receiving unilateral or bilateral HFS of the MD decreased the number of stage 5 EEG seizure synchronized with the convulsive episodes;LFS and sham stimulation showed multiple periods of continuous spikes which accompanied stage 5 or stage 4 seizures.HFS of unilateral or bilateral MD,but not LFS,decreased the seizure stage,the number of clonic movement episodes,and the duration of acute PTZ-induced seizures.The average latency to onsct of myoclonic jerks did not differ among groups.Unilateral and bilateral HFS of the MD had a similar antiepileptie effect.Conclusion HFS of the MD may be of value as a new antiepileptic approach for patients with generalized epilepsy,besides,the seizure model,should be fully considered in clinical application.