Vinogradova Ludmilla V, Kuznetsova Galina D, Shatskova Alla B, van Rijn Clementina M
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
Epilepsia. 2005 Jun;46(6):800-10. doi: 10.1111/j.1528-1167.2005.52604.x.
The effect of systemic administration of the gamma-aminobutyric acid (GABA)-transaminase inhibitor vigabatrin (VGB) on different components of convulsions was tested in the model of audiogenically kindled seizures, which consist of brainstem (running, tonus) and forebrain (clonus) elements.
Audiogenically susceptible rats of Krushinsky-Molodkina (KM), Wistar, and WAG/Rij strains received repeated sound stimulation (60 dB, 10-80 kHz) until kindled audiogenic seizures were reliably elicited. Kindled audiogenic seizures consisted of running, tonic, and generalized clonic phases in KM rats (severe audiogenic seizures) and of running and Racine stage 5 facial/forelimb clonus in Wistar and WAG/Rij rats (moderate seizures). Vehicle, 100, or 200 mg/kg of VGB was intraperitoneally injected 2, 4 and 24 h before the induction of kindled audiogenic seizures.
At both doses, VGB did not change the seizure latency and the duration of running and tonic convulsions, but suppressed clonic ones in all rat strains. In KM rats, the mean duration of posttonic clonus was significantly reduced at 24 h after 100 mg/kg and from 4 h after 200 mg/kg. In Wistar and WAG/Rij rats, the mean duration of facial/forelimb clonus was reduced from 4 and 2 h after 100- and 200-mg/kg administration, respectively; 24 h after the high-dose injection, clonus was completely blocked in all rats of both strains. No difference in efficacy of VGB between Wistar and WAG/Rij rats was observed.
VGB more effectively suppresses clonic convulsions than running and tonic ones in audiogenically kindled rats. It is supposed that this selective anticonvulsive effect of VGB results from different sensitivities of forebrain and brainstem epileptic networks to the presumed GABA enhancement.
在听源性惊厥模型中测试全身给予γ-氨基丁酸（GABA）转氨酶抑制剂氨己烯酸（VGB）对惊厥不同组成部分的影响，该模型由脑干（奔跑、紧张性收缩）和前脑（阵挛）成分组成。
对克鲁申斯基-莫洛迪纳（KM）、Wistar和WAG/Rij品系的听源性敏感大鼠进行反复声音刺激（60分贝，10 - 80千赫），直至可靠地诱发听源性惊厥。在KM大鼠中，听源性惊厥由奔跑、强直性和全身性阵挛期组成（严重听源性惊厥），在Wistar和WAG/Rij大鼠中，由奔跑和拉辛5期面部/前肢阵挛组成（中度惊厥）。在诱发听源性惊厥前2、4和24小时腹腔注射溶剂、100或200毫克/千克的VGB。
在两个剂量下，VGB均未改变惊厥潜伏期以及奔跑和强直性惊厥的持续时间，但在所有大鼠品系中均抑制了阵挛性惊厥。在KM大鼠中，100毫克/千克给药后24小时以及200毫克/千克给药后4小时，强直性阵挛的平均持续时间显著缩短。在Wistar和WAG/Rij大鼠中，100毫克/千克和200毫克/千克给药后分别从4小时和2小时起，面部/前肢阵挛的平均持续时间缩短；高剂量注射后24小时，两个品系的所有大鼠阵挛均完全被阻断。未观察到Wistar和WAG/Rij大鼠之间VGB疗效的差异。
在听源性惊厥大鼠中，VGB抑制阵挛性惊厥比奔跑和强直性惊厥更有效。推测VGB这种选择性抗惊厥作用源于前脑和脑干癫痫网络对假定的GABA增强的不同敏感性。
