Please wait a minute...
浙江大学学报（医学版）
浙江大学学报（医学版）  2015, Vol. 44 Issue (3): 315-322    DOI: 10.3785/j.issn.1008-9292.2015.05.12
原著     
不同波形低频率电刺激对小鼠海马电点燃癫痫的作用比较
陶安风1, 许正浩1,2, 吴承昊1, 汪仪1, 侯伟伟1, 张世红1, 陈忠1
1. 浙江大学药学院药理系, 浙江 杭州 310058;
2. 浙江中医药大学基础医学院, 浙江 杭州 310053
Antiepileptic effect of low-frequency electrical stimulation is waveform-dependent in hippocampal kindled mice
TAO An-feng1, XU Zheng-hao1,2, WU Cheng-hao1, WANG Yi1, HOU Wei-wei1, ZHANG Shi-hong1, CHEN Zhong1
1. Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;
2. College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
 全文: PDF(1493 KB)   HTML ( ) 
摘要：

目的:观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法:采用电点燃刺激法建立小鼠癫痫模型,观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响,并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果:与对照组比较,正弦波低频率电刺激30 s 能降低小鼠海马电点燃癫痫发作等级(2.85 ± 0.27 vs 4.75 ±0.12,P<0.05)、减少大发作概率(53.6% vs 96.5%,P< 0.01)和缩短后放电持续时间[(16.22 ± 1.69)s vs (30.29 ± 1.12)s,P<0.01],而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级(3.58 ± 0.16,P<0.05)、减少大发作概率(66.7%,P<0.01);但对海马后放电持续时间及大发作持续时间无影响(均P>0.05)。此外,电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用(P<0.05或P<0.01),而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。结论:低频率电刺激抗癫痫作用受波形参数的影响,其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。
关键词： 癫痫/治疗;  电刺激疗法;  疾病模型,动物    
Abstract:

Objective: To investigate whether the waveform of electrical stimulus affects the antiepileptic effect of focal low-frequency stimulation (LFS). Methods: The antiepileptic effects of the LFS in sine, monophase square and biphase square waves were investigated in hippocampal kindled mice, respectively. Results: Compared to the control group, sine wave focal LFS(30 s) inhibited seizure stages(2.85±0.27 vs 4.75±0.12,P<0.05), lowered incidence of generalized seizures(53.6% vs 96.5%,P<0.01) and reduced afterdischarge durations[(16.22±1.69)s vs (30.29±1.12)s,P<0.01] in hippocampal kindled mice, while monophase or biphase square wave LFS (30 s) showed no antiepileptic effect. Monophase square LFS(15 min) inhibited seizure stages(3.58 ± 0.16,P<0.05) and incidence of generalized seizures(66.7%,P<0.01), but had weaker inhibitory effect on hippocampal afterdischarge durations than sine wave LFS. In addition, pre-treatment and 3 s but not 10 s post-treatment with sine wave LFS resulted in suppression of evoked seizures(P<0.05 or P<0.01). Conclusion: The antiepileptic effect of LFS is dependent on its waveform. Sine wave may be optimal for closed-loop LFS treatment of epilepsy.
Key words: Epilepsy/therapy    Electric stimulation therapy    Disease models, animal
收稿日期: 2014-11-23 出版日期: 2015-05-25
:  R74  
基金资助:

国家自然科学基金(81302749)
通讯作者: 陈忠(1968-),男,博士,教授,博士生导师,从事神经药理学研究;E-mail:chenzhong@zju.edu.cn;http://orcid.org/0000-0003-4755-9357     E-mail: chenzhong@zju.edu.cn
作者简介: 陶安风(1990-),男,硕士研究生,从事神经药理学研究;E-mail:taoanfeng95@163.com;http://orcid.org/0000-0001-6628-5297
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
陶安风
许正浩
吴承昊
汪仪
侯伟伟
张世红
陈忠

引用本文:

陶安风, 许正浩, 吴承昊, 汪仪, 侯伟伟, 张世红, 陈忠. 不同波形低频率电刺激对小鼠海马电点燃癫痫的作用比较[J]. 浙江大学学报（医学版）, 2015, 44(3): 315-322.

TAO An-feng, XU Zheng-hao, WU Cheng-hao, WANG Yi, HOU Wei-wei, ZHANG Shi-hong, CHEN Zhong. Antiepileptic effect of low-frequency electrical stimulation is waveform-dependent in hippocampal kindled mice. Journal of ZheJiang University(Medical Science), 2015, 44(3): 315-322.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2015.05.12    或    http://www.zjujournals.com/med/CN/Y2015/V44/I3/315

[1] BERG A T. Epilepsy: efficacy of epilepsy surgery: what are the questions today?[J]. Nat Rev Neurol, 2011,7(6):311-312.
[2] GUBELLINI P, SALIN P, KERKERIAN-LE G L, et al. Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior[J]. Prog Neurobiol, 2009,89(1):79-123.
[3] 陈 忠,张世红. 深部脑刺激在神经精神疾病治疗中的应用研究进展[J]. 浙江大学学报: 医学版, 2009,38(6):549-558. CHEN Zhong,ZHANG Shi-hong.Advances in application of deep brain stimulation in treatment of neuropsychological diseases[J]. Journal of Zhejiang University: Medical Sciences, 2009,38(6):549-558.(in Chinese)
[4] FEDDERSEN B, VERCUEIL L, NOACHTAR S, et al. Controlling seizures is not controlling epilepsy: a parametric study of deep brain stimulation for epilepsy[J]. Neurobiol Dis, 2007,27(3):292-300.
[5] RACINE R J. Modification of seizure activity by electrical stimulation: cortical areas[J]. Electroencephalogr Clin Neurophysiol, 1975,38(1):1-12.
[6] GOODMAN J H, BERGER R E, TCHENG T K. Preemptive low-frequency stimulation decreases the incidence of amygdala-kindled seizures[J]. Epilepsia, 2005,46(1):1-7.
[7] ULLAL G R, NINCHOJI T, UEMURA K. Low frequency stimulation induces an increase in after-discharge thresholds in hippocampal and amygdaloid kindling[J]. Epilepsy Res, 1989,3(3):232-235.
[8] ZHU-GE Z B, ZHU Y Y, WU D C, et al. Unilateral low-frequency stimulation of central piriform cortex inhibits amygdaloid-kindled seizures in Sprague-Dawley rats[J]. Neuroscience, 2007,146(3):901-906.
[9] ZHONG K, WU D C, JIN M M, et al. Wide therapeutic time-window of low-frequency stimulation at the subiculum for temporal lobe epilepsy treatment in rats[J]. Neurobiol Dis, 2012,48(1):20-26.
[10] WANG S, WU D C, DING M P, et al. Low-frequency stimulation of cerebellar fastigial nucleus inhibits amygdaloid kindling acquisition in Sprague-Dawley rats[J]. Neurobiol Dis, 2008,29(1):52-58.
[11] XU Z H, WU D C, FANG Q, et al. Therapeutic time window of low-frequency stimulation at entorhinal cortex for amygdaloid-kindling seizures in rats[J]. Epilepsia, 2010,51(9):1861-1864.
[12] YAMAMOTO J, IKEDA A, SATOW T, et al. Low-frequency electric cortical stimulation has an inhibitory effect on epileptic focus in mesial temporal lobe epilepsy[J]. Epilepsia, 2002,43(5):491-495.
[13] WEISS S R, LI X L, ROSEN J B, et al. Quenching: inhibition of development and expression of amygdala kindled seizures with low frequency stimulation[J]. Neuroreport, 1995,6(16):2171-2176.
[14] SOLGER J, HEINEMANN U, BEHR J. Electrical and chemical long-term depression do not attenuate low-Mg2+-induced epileptiform activity in the entorhinal cortex[J]. Epilepsia, 2005,46(4):509-516.
[15] D'ARCANGELO G, PANUCCIO G, TANCREDI V, et al. Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks[J]. Neurobiol Dis, 2005,19(1-2):119-128.
[16] XU Z, WANG Y, JIN M, et al. Polarity-dependent effect of low-frequency stimulation on amygdaloid kindling in rats[J]. Brain Stimul, 2013,6(2):190-197.
[17] FRANKLIN K B J, PAXINOS G. The mouse brain in stereotaxic coordinates[M].2nd ed. San Diego: Academic Press,2001:1.
[18] RACINE R J. Modification of seizure activity by electrical stimulation. II. Motor seizure[J]. Electroencephalogr Clin Neurophysiol, 1972,32(3):281-294.
[19] GARRIGA-CANUT M, SCHOENIKE B, QAZI R, et al. 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure[J]. Nat Neurosci, 2006,9(11):1382-1387.
[20] LIU Y, WANG Y, XU Z, et al. Consecutive 15 min is necessary for focal low frequency stimulation to inhibit amygdaloid-kindling seizures in rats[J]. Epilepsy Res, 2013,106(1-2):47-53.
[21] ZHONG K, WU D C, JIN M M, et al. Wide therapeutic time-window of low-frequency stimulation at the subiculum for temporal lobe epilepsy treatment in rats[J]. Neurobiol Dis, 2012,48(1):20-26.
[22] YING X, WANG Y, LIANG J, et al. Angiopep-conjugated electro-responsive hydrogel nanoparticles: therapeutic potential for epilepsy[J]. Angew Chem Int Ed Engl, 2014,53(46):12436-12440.
[23] WANG Y, XU Z, CHENG H, et al. Low-frequency stimulation inhibits epileptogenesis by modulating the early network of the limbic system as evaluated in amygdala kindling model[J]. Brain Struct Funct, 2014,219(5):1685-1696.
[24] GUBELLINI P, SALIN P, KERKERIAN-LE G L, et al. Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior[J]. Prog Neurobiol, 2009,89(1):79-123.
[25] SKARPAAS T L, MORRELL M J. Intracranial stimulation therapy for epilepsy[J]. Neurotherapeutics, 2009,6(2):238-243.
[26] GOODMAN J H, BERGER R E, TCHENG T K. Preemptive low-frequency stimulation decreases the incidence of amygdala-kindled seizures[J]. Epilepsia, 2005,46(1):1-7.
[27] ZHANG S H, SUN H L, FANG Q, et al. Low-frequency stimulation of the hippocampal CA3 subfield is anti-epileptogenic and anti-ictogenic in rat amygdaloid kindling model of epilepsy[J]. Neurosci Lett, 2009,455(1):51-55.
[28] BERENYI A, BELLUSCIO M, MAO D, et al. Closed-loop control of epilepsy by transcranial electrical stimulation[J]. Science, 2012,337(6095):735-737.
[29] PATEL J, SCHOMBURG E W, BERENYI A, et al. Local generation and propagation of ripples along the septotemporal axis of the hippocampus[J]. J Neurosci, 2013,33(43):17029-17041.
[30] TRUCCOLO W, DONOGHUE J A, HOCHBERG L R, et al. Single-neuron dynamics in human focal epilepsy[J]. Nat Neurosci, 2011,14(5):635-641.
[31] KROOK-MAGNUSON E, ARMSTRONG C, OIJALA M, et al. On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy[J]. Nat Commun, 2013,4:1376.
[1] 刘扬, 汪仪, 许正浩, 陈忠. 低频率电刺激抑制杏仁核电点燃癫痫刺激模式依赖效应的实验研究[J]. 浙江大学学报（医学版）, 2015, 44(5): 539-545.
[2] 陈忠;张世红. 深部脑刺激在神经精神疾病治疗中的应用研究进展[J]. 浙江大学学报（医学版）, 2009, 38(6): 549-558.
[3] 吴海琴;姚丽;杜赟;张桂莲;张茹;刘璟洁;卜宁. Ref-1在阿尔茨海默病大鼠海马CA1区表达的研究[J]. 浙江大学学报（医学版）, 2008, 37(6): 629-633.