Chou Ping, Kuo Chung-Chin
Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Front Syst Neurosci. 2021 Aug 2;15:607450. doi: 10.3389/fnsys.2021.607450. eCollection 2021.
Since deep brain stimulation (DBS) at the epileptogenic focus () denotes long-term repetitive stimulation of the potentially epileptogenic structures, such as the amygdala, the hippocampus, and the cerebral cortex, a kindling effect and aggravation of seizures may happen and complicate the clinical condition. It is, thus, highly desirable to work out a protocol with an evident quenching (anticonvulsant) effect but free of concomitant proconvulsant side effects. We found that in the basolateral amygdala (BLA), an extremely wide range of pulsatile stimulation protocols eventually leads to the kindling effect. Only protocols with a pulse frequency of ≤1 Hz or a direct current (DC), with all of the other parameters unchanged, could never kindle the animal. On the other hand, the aforementioned DC stimulation (DCS), even a pulse as short as 10 s given 5 min before the kindling stimuli or a pulse given even to the contralateral BLA, is very effective against epileptogenicity and ictogenicity. Behavioral, electrophysiological, and histological findings consistently demonstrate success in seizure quenching or suppression as well as in the safety of the specific DBS protocol (e.g., no apparent brain damage by repeated sessions of stimulation applied to the BLA for 1 month). We conclude that DCS, with a novel and rational design of the stimulation protocol composed of a very low (∼3% or 10 s/5 min) duty cycle and assuredly devoid of the potential of kindling, may make a successful antiepileptic therapy with adequate safety in terms of little epileptogenic adverse events and tissue damage.
由于在致痫灶进行深部脑刺激（DBS）意味着对潜在的致痫结构（如杏仁核、海马体和大脑皮层）进行长期重复刺激，可能会发生点燃效应并加重癫痫发作，从而使临床情况复杂化。因此，非常需要制定一种具有明显抑制（抗惊厥）作用且无伴随的促惊厥副作用的方案。我们发现，在基底外侧杏仁核（BLA）中，极广泛的脉冲刺激方案最终都会导致点燃效应。只有脉冲频率≤1Hz的方案或直流电（DC），在所有其他参数不变的情况下，永远不会使动物产生点燃效应。另一方面，上述直流电刺激（DCS），即使在点燃刺激前5分钟给予短至10秒的脉冲，或甚至给予对侧BLA的脉冲，对致痫性和发作性都非常有效。行为学、电生理学和组织学研究结果一致表明，在癫痫发作抑制或抑制方面以及在特定DBS方案的安全性方面（例如，对BLA进行1个月的重复刺激 sessions未造成明显脑损伤）均取得了成功。我们得出结论，DCS采用新颖合理的刺激方案设计，占空比极低（约3%或10秒/5分钟）且肯定没有点燃的可能性，在癫痫源性不良事件和组织损伤较少的情况下，可能会成为一种具有足够安全性的成功抗癫痫治疗方法。
