癫痫杂志

癫痫杂志

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

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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。

ObjectiveThe 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 effect of high frequency stimulation in MD on pentylenetetrazole (PTZ)-induced seizures in rats. MethodsThe 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). EEGs in the cortex and seizure behavior were recorded with the Neuroscan system at the same time. ResultsNeither 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 onset of myoclonic jerks did not differ among groups. Unilateral and bilateral HFS of the MD had a similar antiepileptic effect. ConclusionHFS 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.

关键词: 癫痫; 深部脑刺激; 丘脑背内侧核团; 全面性癫痫; 大鼠

Key words: Epilepsy; Deep brain stimulation; Mediodorsal thalamic nucleus; Generalized seizures; Rats

引用本文: 朱露佳, 吴登唱, 丁美萍, 陈忠, 王爽. 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. 癫痫杂志, 2016, 2(5): 387-392. doi: 10.7507/2096-0247.20160068 复制

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1. Salanova V, Witt T, Worth R, et al. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology, 2015, 84(10):1017-1025.
2. Bertram EH, Mangan PS, Zhang D, et al. The midline thalamus:alterations and a potential role in limbic epilepsy. Epilepsia, 2001, 42(8):967-978.
3. Bertram EH, Zhang D, Williamson JM. Multiple roles of midline dorsal thalamic nuclei in induction and spread of limbic seizures. Epilepsia, 2008, 49(2):256-268.
4. Blumenfeld H, Rivera M, Vasquez JG, et al. Neocortical and thalamic spread of amygdala kindled seizures. Epilepsia, 2007, 48(2):254-262.
5. Rajasekaran K, Kapur J, Bertram EH. Alterations in GABA(A) receptor mediated inhibition in adjacent dorsal midline thalamic nuclei in a rat model of chronic limbic epilepsy. J Neurophysiol, 2007, 98(5):2501-2508.
6. Shehab S, Coffey P, Dean P, et al. Regional expression of fos-like immunoreactivity following seizures induced by pentylenetetrazole and maximal electroshock. Exp Neurol, 1992, 118(3):261-274.
7. Nishida N, Huang ZL, Mikuni N, et al. Deep brain stimulation of the posterior hypothalamus activates the histaminergic system to exert antiepileptic effect in rat pentylenetetrazol model. Exp Neurol, 2007, 205(1):132-144.
8. Racine RJ. Modification of seizure activity by electrical stimulation after-discharge threshold. Electroencephalogr Clin Neurophysiol, 1972, 32(3):269-279.
9. Eells JB, Clough RW, Browning RA, et al. Comparative fos immunoreactivity in the brain after forebrain, brainstem, or combined seizures induced by electroshock, pentylenetetrazol, focally induced and audiogenic seizures in rats. Neuroscience, 2004, 123(1):279-292.
10. Brevard ME, Kulkarni P, King JA, et al. Imaging the neural substrates involved in the genesis of pentylenetetrazol-induced seizures. Epilepsia, 2006, 47(4):745-754.
11. Li XB, Inoue T, Nakagawa S, et al. Effect of mediodorsal thalamic nucleus lesion on contextual fear conditioning in rats. Brain Res, 2004, 1008(2):261-272.
12. Groenewegen HJ. Organization of the afferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography. Neuroscience, 1988, 24(2):379-431.
13. Krettek JE, Price JL. The cortical projections of the mediodorsal nucleus and adjacent thalamic nuclei in the rat. J Comp Neurol, 1977, 171(2):157-191.
14. Ray JP, Price JL. The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys. J Comp Neurol, 1993, 337(1):1-31.
15. Cavalheiro EA, Leite JP, Bortolotto ZA, et al. Long-term effects of pilocarpine in rats:structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia, 1991, 32(6):778-782.
16. Sinjab B, Martinian L, Sisodiya SM, et al. Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy:a postmortem study. Epilepsia, 2013, 54(12):2125-2133.
17. Cassidy RM, Gale K. Mediodorsal thalamus plays a critical role in the development of limbic motor seizures. J Neurosci, 1998, 18(21):9002-9009.
18. Hirayasu Y, Wada JA. N-methyl-D-aspartate injection into the massa intermedia facilitates development of limbic kindling in rats. Epilepsia, 1992, 33(6):965-970.
19. Patel S, Millan MH, Meldrum BS. Decrease in excitatory transmission within the lateral habenula and the mediodorsal thalamus protects against limbic seizures in rats. Exp Neurol, 1988, 101(1):63-74.
20. Mirski MA, Rossell LA, Terry JB, et al. Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat. Epilepsy Res, 1997, 28(2):89-100.
21. Negyessy L, Hamori J, Bentivoglio M. Contralateral cortical projection to the mediodorsal thalamic nucleus:origin and synaptic organization in the rat. Neuroscience, 1998, 84(3):741-753.
22. McIntyre CC, Savasta M, Kerkerian-Le Goff L, et al. Uncovering the mechanism(s) of action of deep brain stimulation:activation, inhibition, or both. Clin Neurophysiol, 2004, 115(6):1239-1248.
23. Bikson M, Lian J, Hahn PJ, et al. Suppression of epileptiform activity by high frequency sinusoidal fields in rat hippocampal slices. J Physiol, 2001, 531(Pt 1):181-191.
24. Lian J, Bikson M, Sciortino C, et al. Local suppression of epileptiform activity by electrical stimulation in rat hippocampus in vitro. J Physiol, 2003, 547(Pt 2):427-434.
25. Durand DM, Jensen A, Bikson M. Suppression of neural activity with high frequency stimulation. Conf Proc IEEE Eng Med Biol Soc, 2006, 1:1624-1625.
26. Nanobashvili Z, Chachua T, Nanobashvili A, et al. Suppression of limbic motor seizures by electrical stimulation in thalamic reticular nucleus. Exp Neurol, 2003, 181(2):224-230.
27. Velasco M, Velasco F, Velasco AL, et al. Acute and chronic electrical stimulation of the centromedian thalamic nucleus:modulation of reticulo-cortical systems and predictor factors for generalized seizure control. Arch Med Res, 2000, 31(3):304-315.
28. Schiller Y, Bankirer Y. Cellular mechanisms underlying antiepileptic effects of low-and high-frequency electrical stimulation in acute epilepsy in neocortical brain slices in vitro. J Neurophysiol, 2007, 97(3):1887-1902.
29. Wang S, Wu DC, Ding MP, et al. Low-frequency stimulation of cerebellar fastigial nucleus inhibits amygdaloid kindling acquisition in Sprague-Dawley rats. Neurobiol Dis, 2008, 29(1):52-58.
30. Zhang de X, Bertram EH. Suppressing limbic seizures by stimulating medial dorsal thalamic nucleus:factors for efficacy. Epilepsia, 2015, 56(3):479-488.