Characteristics of flurothyl-induced seizures and the evaluation of the model of development of epilepsy

1)在氟乙烯点燃模型中，8次氟乙烯诱导的全身性阵挛性癫痫发作（称为前脑癫痫发作）和随后的28天无刺激间隔将小鼠的癫痫发作表型从纯粹的前脑癫痫发作改变为更复杂表型的癫痫发作。当用氟乙烯再次激发时，全身性发作的前脑癫痫发作迅速发展为强直性表现的癫痫发作，称为脑干癫痫发作。2）当在氟乙烯试验前8天每天给予小鼠丙戊酸盐、唑尼沙胺和苯妥英时，丙戊酸盐和唑尼沙胺显著抑制了癫痫发作表型从阵挛性到强直性的变化，3）MK-801对小鼠的急性作用中，对小鼠的阵挛性发作的潜伏期无明显影响。然而，MK-801剂量依赖性地抑制小鼠的癫痫发作和强直性癫痫发作的发生率，并抑制氟乙烯点燃小鼠的癫痫发作严重程度。此外，MK-801重复给药对阵挛性癫痫发作的潜伏期无任何影响。然而，当小鼠在末次给药后1周再次暴露于氟罗泰（不含MK-801）时，癫痫发作严重程度显著加重。4）蒙古沙鼠在阵挛性惊厥出现后1 min内立即表现出强直性伸展。在癫痫发作的同时，皮层、海马和杏仁核出现极高幅值的棘波。5）6-OHDA和DSP-4给药小鼠的癫痫模式没有改变。这一发现与电点燃模型完全不同。

1) In the flurothyl kindling model, eight flurothyl-induced generalized clonic seizures, dubbed forebrain seizures, and a subsequent 28-days stimulation-free interval changed the seizure phenotype of mice from purely forebrain seizure to seizures of a more complex phenotype. The generalized-onset, forebrain seizure progresses rapidly to a seizure with tonic manifestations, dubbed brain-stem seizures, when re-challenged with flurothyl.2) When valproate, zonisamide and phenytoin were administered to mice daily for 8 d prior to the flurothyl trial changes in the seizure phenotype from clonic to tonic seizure were significantly inhibited by valproate and zonisamide, but not by phenytoin.3) In the acute effect of MK-801 in naive and flurothyl-kindled mice, there were no changes on the latencies of clonic seizures. However, MK-801 dose-dependently inhibited both latencies and the incidence of tonic seizures in mice and suppressed the grade of seizure severity in flurothyl-kindled mice. In addition, repeated administration of MK-801 did not have any effect on the latencies of clonic seizure. However, seizure severity was significantly exacerbated when mice were re-exposed to flurothyl without MK-801 1 week after the last administration.4) Mongolian gerbils demonstrated tonic extension immediately after within 1 min after the appearance of clonic convulsion. Very high amplitude spike waves appeared in the cortex, hippocampus and amygdala concurrent with the appearance of clonic convulsion.5) The epilepsy pattern was not changed in 6-OHDA- and DSP-4-administered mice. This finding is completely different with electrical kindling model.