Schiller Yitzhak, Bankirer Yael
Department of Neurology, Rambam Medical Center, 1 Efron St., Haifa 31096, Israel.
J Neurophysiol. 2007 Mar;97(3):1887-902. doi: 10.1152/jn.00514.2006. Epub 2006 Dec 6.
Approximately 30% of epilepsy patients suffer from drug-resistant epilepsy. Direct electrical stimulation of the epileptogenic zone is a potential new treatment modality for this devastating disease. In this study, we investigated the effect of two electrical stimulation paradigms, sustained low-frequency stimulation and short trains of high-frequency stimulation, on epileptiform discharges in neocortical brain slices treated with either bicuculline or magnesium-free extracellular solution. Sustained low-frequency stimulation (5-30 min of 0.1- to 5-Hz stimulation) prevented both interictal-like discharges and seizure-like events in an intensity-, frequency-, and distance-dependent manner. Short trains of high-frequency stimulation (1-5 s of 25- to 200-Hz stimulation) prematurely terminated seizure-like events in a frequency-, intensity-, and duration-dependent manner. Roughly one half the seizures terminated within the 100-Hz stimulation train (P < 0.01 compared with control), whereas the remaining seizures were significantly shortened by 53 +/- 21% (P < 0.01). Regarding the cellular mechanisms underlying the antiepileptic effects of electrical stimulation, both low- and high-frequency stimulation markedly depressed excitatory postsynaptic potentials (EPSPs). The EPSP amplitude decreased by 75 +/- 3% after 10-min, 1-Hz stimulation and by 86 +/- 6% after 1-s, 100-Hz stimulation. Moreover, partial pharmacological blockade of ionotropic glutamate receptors was sufficient to suppress epileptiform discharges and enhance the antiepileptic effects of stimulation. In conclusion, this study showed that both low- and high-frequency electrical stimulation possessed antiepileptic effects in the neocortex in vitro, established the parameters determining the antiepileptic efficacy of both stimulation paradigms, and suggested that the antiepileptic effects of stimulation were mediated mostly by short-term synaptic depression of excitatory neurotransmission.
约30%的癫痫患者患有药物难治性癫痫。直接电刺激致痫区是治疗这种毁灭性疾病的一种潜在新方法。在本研究中，我们研究了两种电刺激模式，即持续低频刺激和短串高频刺激，对用荷包牡丹碱或无镁细胞外溶液处理的新皮质脑片癫痫样放电的影响。持续低频刺激（0.1至5赫兹刺激5至30分钟）以强度、频率和距离依赖性方式预防了发作间期样放电和癫痫样发作。短串高频刺激（25至200赫兹刺激1至5秒）以频率、强度和持续时间依赖性方式提前终止癫痫样发作。大约一半的癫痫发作在100赫兹刺激串内终止（与对照组相比，P<0.01），而其余癫痫发作明显缩短了53±21%（P<0.01）。关于电刺激抗癫痫作用的细胞机制，低频和高频刺激均显著抑制兴奋性突触后电位（EPSP）。10分钟1赫兹刺激后EPSP幅度降低75±3%，1秒100赫兹刺激后降低86±6%。此外，离子型谷氨酸受体的部分药理学阻断足以抑制癫痫样放电并增强刺激的抗癫痫作用。总之，本研究表明低频和高频电刺激在体外新皮质均具有抗癫痫作用，确定了两种刺激模式抗癫痫疗效的参数，并提示刺激的抗癫痫作用主要由兴奋性神经传递的短期突触抑制介导。
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