Mares Pavel, Slamberová Romana
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Mar;369(3):305-11. doi: 10.1007/s00210-004-0865-1. Epub 2004 Feb 7.
The time course of the anticonvulsant effect of vigabatrin against cortically induced epileptic after-discharges (ADs) was studied in freely moving rats with implanted electrodes. Adult rats (n=30) were exposed to five stimulation sessions each consisting of six stimulation series at 20-min intervals. The first session was a control one, then two groups of animals (n=10 each) were given vigabatrin (600 or 1,200 mg/kg i.p.), the control animals received physiological saline. Stimulation sessions were repeated 1, 24, 48, and 96 hours after the injection. Control animals exhibited an increased transition from the spike-and-wave type of AD to the second, "limbic" type and an increased intensity of movements accompanying stimulation. ADs in the second and subsequent sessions were, however, shorter than in the first session. Vigabatrin facilitated the transition to the second type of AD 1 h after administration but suppressed this transition as well as decreased the number of stimulations eliciting ADs 48 h later. AD duration and the severity of clonic seizures accompanying spike-and-wave ADs were influenced similarly. The effects of the lower dose of vigabatrin were more marked than those of the higher dose. The biphasic action of vigabatrin in our model might be due either to uneven changes of GABA concentration in different brain structures or to an additional mechanism of action. Our results in a cortical model of seizure demonstrate that the sequence of pro- and anticonvulsant actions of vigabatrin is not restricted to seizures of limbic origin and might represent a general phenomenon.
在植入电极的自由活动大鼠中研究了氨己烯酸对皮层诱导癫痫后放电（ADs）的抗惊厥作用的时程。成年大鼠（n = 30）接受五个刺激时段，每个时段由六个间隔20分钟的刺激系列组成。第一个时段为对照时段，然后两组动物（每组n = 10）给予氨己烯酸（腹腔注射600或1200 mg/kg），对照动物接受生理盐水。在注射后1、24、48和96小时重复刺激时段。对照动物表现出从尖波型AD向第二种“边缘”型的转变增加，以及伴随刺激的运动强度增加。然而，第二个及后续时段的ADs比第一个时段短。氨己烯酸在给药后1小时促进向第二种AD类型的转变，但在48小时后抑制这种转变并减少引发ADs的刺激次数。AD持续时间以及伴随尖波ADs的阵挛性癫痫发作的严重程度受到类似影响。较低剂量氨己烯酸的作用比较高剂量更明显。氨己烯酸在我们模型中的双相作用可能是由于不同脑结构中GABA浓度的不均匀变化或额外的作用机制。我们在癫痫皮层模型中的结果表明，氨己烯酸的促惊厥和抗惊厥作用顺序不仅限于边缘性癫痫发作，可能是一种普遍现象。
