John Jenine E, Baptiste Shirn L, Sheffield Lynette G, von Gizycki Hans, Kuzniecky Ruben I, Devinsky Orrin, Ludvig Nandor
Comprehensive Epilepsy Center, Department of Neurology, NYU School of Medicine, New York, NY 10016, USA.
Epilepsy Res. 2007 Jun;75(1):10-7. doi: 10.1016/j.eplepsyres.2007.03.014. Epub 2007 May 2.
Transmeningeal drug delivery, using an implanted hybrid neuroprosthesis, has been proposed as a novel therapy for intractable focal epilepsy. As part of a systematic effort to identify the optimal compounds and protocols for such a therapy, this study aimed to determine whether transmeningeal gamma-aminobutyric acid (GABA) delivery can terminate and/or prevent neocortical seizures in rats. Rats were chronically implanted with an epidural cup and an adjacent EEG electrode in the right parietal cortex. While the rat was behaving freely, a seizure-inducing concentration of acetylcholine (Ach) was applied into the cup. In a seizure termination study, either artificial cerebrospinal fluid (ACSF) or GABA (0.25, 2.5, 25 or 50mM) was delivered into the exposed neocortical area during an ongoing seizure. In a seizure prevention study, either ACSF or 50mM GABA was delivered into the epidural cup before the application of Ach. Epidural delivery of 50mM GABA completely terminated ongoing Ach-induced EEG seizures and convulsions within 17-437s after its delivery. ACSF and lower concentrations of GABA did not produce this effect, but 25mM GABA reduced seizure severity. However, the used GABA concentration could not prevent the development, or affect the severity, of Ach-induced EEG seizures and convulsions. This study indicates that transmeningeal GABA delivery can be used for terminating neocortical seizures, but to achieve seizure prevention via this route either a more efficient GABA delivery method needs to be developed or other neurotransmitters/pharmaceuticals should be employed for this purpose.
利用植入式混合神经假体进行经脑膜给药，已被提议作为治疗顽固性局灶性癫痫的一种新疗法。作为确定此类疗法的最佳化合物和方案的系统努力的一部分，本研究旨在确定经脑膜递送γ-氨基丁酸（GABA）是否能终止和/或预防大鼠新皮质癫痫发作。大鼠在右侧顶叶皮质长期植入硬膜外杯和相邻的脑电图电极。当大鼠自由活动时，将诱发癫痫发作浓度的乙酰胆碱（Ach）注入杯中。在癫痫发作终止研究中，在癫痫发作持续期间，将人工脑脊液（ACSF）或GABA（0.25、2.5、25或50mM）递送至暴露的新皮质区域。在癫痫发作预防研究中，在应用Ach之前将ACSF或50mM GABA注入硬膜外杯。硬膜外递送50mM GABA在递送后17 - 437秒内完全终止了正在进行的Ach诱导的脑电图癫痫发作和惊厥。ACSF和较低浓度的GABA没有产生这种效果，但25mM GABA降低了癫痫发作的严重程度。然而，所用的GABA浓度不能预防Ach诱导的脑电图癫痫发作和惊厥的发生，也不影响其严重程度。本研究表明，经脑膜递送GABA可用于终止新皮质癫痫发作，但要通过该途径实现癫痫发作预防，要么需要开发更有效的GABA递送方法，要么应为此目的使用其他神经递质/药物。
