Pharmacobiology Department, Center for Research and Advanced Studies, Calz. Tenorios 235, Col. Granjas Coapa, Mexico City 14330, Mexico.
Pharmacol Ther. 2013 May;138(2):211-28. doi: 10.1016/j.pharmthera.2013.01.009. Epub 2013 Jan 24.
In spite of the high success rate of many surgical procedures for pharmacoresistant epilepsy, a substantial number of patients do not become seizure-free. Different strategies for electrical modulation of the brain such as Deep Brain Stimulation, Vagal Nerve Stimulation and Transcraneal Magnetic Stimulation have gained considerable interest in the last decade as alternative therapies for patients with medically refractory epilepsy. Research into the mechanism of action of the strategies for electrical modulation of the brain suggests a crucial role of different molecules and channels such as glutamate, γ-aminobutyric acid, adenosine, brain-derived neurotrophic factor, calcium channels, sodium channels as well as extracellular potassium. Electrical modulation of the brain may reduce the overexpression of P-glycoprotein, a drug efflux transporter that reduces the absorption of antiepileptic drugs. Electrical modulation of the brain induces long-term effects associated with beneficial consequences on clinical symptoms observed during the postictal state. In addition, electrical modulation of the brain might also promote the neurogenesis in subjects with pharmacoresistant epilepsy in whom this process is decreased. Targeting the regulatory pathways in charge of the effects of electrical modulation of the brain is discussed as a means to improve its efficacy. Electrical modulation of the brain combined with pharmacotherapy may represent an innovative approach to avoid epileptogenesis, reduce seizure activity, induce beneficial effects during the postictal state, diminish the amount of antiepileptic drugs, and improve alertness, memory and mood in pharmacoresistant epilepsy.
尽管许多抗药性癫痫的手术成功率很高，但仍有相当数量的患者无法完全摆脱癫痫发作。在过去十年中，作为对药物难治性癫痫患者的替代疗法，对大脑电调制的不同策略（如深部脑刺激、迷走神经刺激和经颅磁刺激）引起了相当大的兴趣。对大脑电调制策略的作用机制的研究表明，不同分子和通道（如谷氨酸、γ-氨基丁酸、腺苷、脑源性神经营养因子、钙通道、钠通道以及细胞外钾）起着至关重要的作用。大脑电调制可能会降低 P-糖蛋白的过度表达，P-糖蛋白是一种药物外排转运体，可降低抗癫痫药物的吸收。大脑电调制会产生长期影响，并与癫痫发作后状态下观察到的临床症状的有益后果相关。此外，大脑电调制还可能促进耐药性癫痫患者的神经发生，而这一过程在这些患者中会减少。针对负责大脑电调制效果的调节途径的靶向治疗被认为是提高其疗效的一种手段。大脑电调制结合药物治疗可能代表一种避免癫痫发生、减少癫痫发作活动、在癫痫发作后状态下产生有益效果、减少抗癫痫药物用量以及改善耐药性癫痫患者的警觉性、记忆力和情绪的创新方法。
