Ferland R J, Applegate C D
Department of Neurology, University of Rochester School of Medicine and Dentistry, New York, USA.
Epilepsia. 1999 Feb;40(2):144-52. doi: 10.1111/j.1528-1157.1999.tb02067.x.
This study sought to determine whether there was a transfer of seizure susceptibility between two models of epileptogenesis, electrical kindling and a newly described model of flurothyl kindling. In this study, we determined the effects of preexposure to one kindling agent on the seizure responsiveness to the other.
Mice were divided into three groups: (a) six mice (FLK) were kindled with flurothyl, rechallenged with flurothyl after a 28-day incubation phase, implanted with olfactory bulb (OB) electrodes, and electrically kindled; (b) six mice (ELK) were implanted with OB electrodes, electrically kindled to six stage 5 seizures, and given one flurothyl trial 3 days later and a second flurothyl trial after a 28-day incubation period; and (c) six mice (IMP) were implanted with OB electrodes, tested with flurothyl at the same times as the ELK group, and later electrically kindled.
Mice that were previously kindled with flurothyl (FLK) had significantly faster electrical kindling rates to one stage 5 seizure or to six stage 5 seizures compared with animals in the ELK and IMP groups. Mice that were previously exposed to either electrical kindling or flurothyl kindling had significantly diminished latencies to generalized seizure onset (flurothyl-induced seizure thresholds) either before or after a 28-day incubation period compared with the IMP control mice. In addition, both the FLK and ELK groups had significantly increased percentages of mice expressing forebrain-brainstem seizures, compared with the IMP group, following either rechallenge with flurothyl after a 28-day incubation or focal electrical kindling.
These findings indicate a near-complete bidirectional transfer between these electrical and flurothyl kindling models. Mice that were previously exposed to either electrical or flurothyl kindling have increased seizure susceptibilities and altered seizure phenotypes when exposed to the other seizure paradigm. Overall, these studies indicate that previous seizures are the critical determinant of the bidirectional transfer of seizure susceptibility observed, and not the electrical or pharmacologic properties of the original kindling agent. Finally, the observation of near identity in transfer characteristics between electrical and flurothyl kindling models suggests that the proepileptogenic processes initiated by exposure to either model are similar.
本研究旨在确定在两种癫痫发生模型（电刺激点燃和新描述的氟烷点燃模型）之间是否存在癫痫发作易感性的转移。在本研究中，我们确定了预先暴露于一种点燃剂对另一种点燃剂引起的癫痫发作反应性的影响。
将小鼠分为三组：(a) 六只小鼠（氟烷点燃组，FLK）用氟烷点燃，在28天的潜伏期后用氟烷再次激发，植入嗅球（OB）电极，然后进行电刺激点燃；(b) 六只小鼠（电刺激点燃组，ELK）植入OB电极，电刺激点燃至六次5级发作，3天后进行一次氟烷试验，28天潜伏期后进行第二次氟烷试验；(c) 六只小鼠（植入对照组，IMP）植入OB电极，在与ELK组相同的时间用氟烷进行测试，随后进行电刺激点燃。
与ELK组和IMP组的动物相比，先前用氟烷点燃的小鼠（FLK）达到一次5级发作或六次5级发作的电刺激点燃速率明显更快。与IMP对照组小鼠相比，先前暴露于电刺激点燃或氟烷点燃的小鼠在28天潜伏期前后全身性癫痫发作起始的潜伏期（氟烷诱导的癫痫发作阈值）均显著缩短。此外，与IMP组相比，在28天潜伏期后用氟烷再次激发或进行局灶性电刺激点燃后，FLK组和ELK组中表达前脑 - 脑干癫痫发作的小鼠百分比均显著增加。
这些发现表明在这些电刺激和氟烷点燃模型之间存在近乎完全的双向转移。先前暴露于电刺激或氟烷点燃的小鼠在暴露于另一种癫痫发作范式时，癫痫发作易感性增加且癫痫发作表型改变。总体而言，这些研究表明先前的癫痫发作是观察到的癫痫发作易感性双向转移的关键决定因素，而非原始点燃剂的电学或药理学特性。最后，电刺激和氟烷点燃模型之间转移特征近乎相同的观察结果表明，暴露于任何一种模型所引发的致癫痫过程是相似的。
