Activation of long-term synaptic plasticity causes suppression of epileptiform activity in rat hippocampal slices
Activation of long-term synaptic plasticity causes suppression of epileptiform activity in rat hippocampal slices
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DOI：
10.1016/j.brainres.2003.11.010
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发表时间：
2004-02-13
期刊：
影响因子：
2.9
通讯作者：
Janigro, D
中科院分区：
文献类型：
--
作者：
Albensi, BC;Ata, G;Janigro, D
用于治疗癫痫的大脑靶点的电刺激是一个正在积极研究的领域。最近的研究表明，在动物模型和顽固性癫痫患者中，长期刺激丘脑底核、穹窿或海马可能有效减少癫痫发作频率。然而，存在许多问题，例如具体的电参数、目标部位和机制等是什么，在考虑对癫痫患者常规使用慢性刺激之前，应该在动物研究中进行研究。了解重复脉冲刺激期间以及刺激后神经活动发生的情况也很重要。为此，我们假设：（1）突触可塑性的激活抑制癫痫样活动；（2）低频刺激是降低癫痫发作强度和频率的有效刺激方案。我们使用大鼠海马脑切片来研究电刺激如何影响自发性和诱发性癫痫样活动。此外，我们还比较了相同制剂中的低频率（1 Hz）与高频率（100 Hz）刺激。我们发现顺向刺激 Schaffer 络脉 10 分钟会降低正常反应的幅度并减少癫痫样活动。 1 Hz 刺激的抑制作用是渐进的，但持续的，而 100 Hz 刺激的抑制作用是快速的；然而，100 Hz 刺激的效果是短暂的。最后，NMDA 拮抗剂 AP5 逆转了 1 Hz 刺激所达到的抗癫痫作用。总的来说，这些数据表明，使用不同的刺激参数对海马进行长时间的电刺激可能会有效降低癫痫患者的癫痫发作频率，并且低频刺激的抑制可能是由长期抑郁（LTD）介导的。 (C) 2003 Elsevier B.V. 保留所有权利。
Electrical stimulation of cerebral targets for the treatment of epilepsy is an area under active investigation. Recent studies have shown that chronic stimulation of the subthalamic nucleus, fornix, or hippocampus may be effective in attenuating seizure frequency in animal models and in patients with intractable epilepsy. However, many questions exist, such as what are the specific electrical parameters, target sites, and mechanisms, etc., which should be investigated in animal studies before considering the routine use of chronic stimulation in epileptic patients. It is also important to understand what happens to neural activity during repetitive pulse stimulation as well as after stimulation. To this end, we hypothesized: (1) activation of synaptic plasticity suppresses epileptiform activity and (2) low frequency stimulation is an effective stimulation protocol for reducing seizure intensity and frequency. We used rat hippocampal brain slices to study how electrical stimulation affects spontaneous and evoked epileptiform activity. Further, we compared low (I Hz) versus high (100 Hz) frequency stimulation in the same preparation. We found that orthodromic stimulation of the Schaffer collaterals for 10 min reduces the amplitude of normal responses and diminishes epileptiform activity. The onset of suppression by I Hz stimulation was gradual, but persistent, whereas the onset of suppression by 100 Hz was rapid; however, the effects of 100 Hz stimulation were transient. Finally, the NMDA antagonist, AP5 reversed the antiepileptic effects achieved by I Hz stimulation. Collectively, these data suggest that using different stimulation parameters prolonged electrical stimulation in the hippocampus may be effective in reducing seizure frequency in patients with epilepsy and that suppression by low frequency stimulation may be mediated by long-term depression (LTD). (C) 2003 Elsevier B.V. All rights reserved.