Mazarati A M, Baldwin R A, Sankar R, Wasterlain C G
Department of Neurology, UCLA School of Medicine, Los Angeles, CA,
Brain Res. 1998 Dec 14;814(1-2):179-85. doi: 10.1016/s0006-8993(98)01080-4.
An animal model of self-sustaining status epilepticus (SSSE) induced in rats by brief intermittent perforant path stimulation (PPS) was examined with regard to the effects of two conventional antiepileptic drugs, diazepam and phenytoin. Thirty or sixty minutes PPS induced SSSE characterized by continuous behavioral and electrographic seizures lasting for hours. Both diazepam (10 mg/kg i. v.) and phenytoin (50 mg/kg i.v.) prevented the establishment of SSSE when administered 10 min prior to PPS. The injection of diazepam to seizing animals, 10 min after the end of 30 min PPS, was significantly less effective than pretreatment in attenuating SSSE. Administration of diazepam after 60 min PPS was characterized by a further decrease of its efficacy. Phenytoin was effective in aborting SSSE when injected 10 min after 30 min PPS. However, its efficacy was vastly decreased if injected 40 min after 30 min PPS, or 10 min after 60 min PPS. It is concluded that antiepileptic drugs, while highly effective in blocking the induction of SSSE, failed to affect its maintenance. SSSE induced by PPS is an advantageous animal model of refractory status epilepticus, which may be used in preclinical studies of novel antiepileptic drugs.
通过短暂间歇性穿通路径刺激（PPS）在大鼠中诱导出自我维持性癫痫持续状态（SSSE）的动物模型，研究了两种传统抗癫痫药物地西泮和苯妥英钠的作用。30或60分钟的PPS诱导出以持续数小时的连续行为和脑电图癫痫发作为特征的SSSE。在PPS前10分钟给药时，地西泮（10毫克/千克静脉注射）和苯妥英钠（50毫克/千克静脉注射）均能预防SSSE的发生。在30分钟PPS结束后10分钟给正在发作的动物注射地西泮，在减轻SSSE方面明显不如预处理有效。在60分钟PPS后给予地西泮，其疗效进一步降低。在30分钟PPS后10分钟注射苯妥英钠可有效终止SSSE。然而，如果在30分钟PPS后40分钟或60分钟PPS后10分钟注射，其疗效会大幅降低。结论是，抗癫痫药物虽然在阻断SSSE的诱导方面非常有效，但未能影响其维持。PPS诱导的SSSE是难治性癫痫持续状态的一种有利动物模型，可用于新型抗癫痫药物的临床前研究。
