Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy
Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy
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DOI：
10.1016/s0920-1211(01)00302-3
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发表时间：
2001-12-01
影响因子：
2.2
通讯作者：
White, HS
中科院分区：
文献类型：
--
作者：
Barton, ME;Klein, BD;White, HS
最初被描述为‘精神运动性癫痫’的模型(J.Pharmacol)。实验在那里。(1953)，由于对苯妥英钠缺乏敏感性，6赫兹角膜刺激模型在被描述后不久就被放弃了。这一观察结果是本研究的基础，旨在验证6赫兹发作作为难治性癫痫模型的有效性。在不同的电流强度下，使用7种已建立的抗癫痫药物(苯妥英、卡马西平、氯硝西潘、苯巴比妥、乙硫胺、三甲二酮、丙戊酸)和5种第二代抗癫痫药物(拉莫三嗪、左乙拉西坦、非氨基甲酸酯、替加他滨、托吡酯)，测定6赫兹癫痫发作的药理学特征。即刻早期基因c-Fos被用作癫痫诱导的神经元激活的标志，以帮助确定由6赫兹角膜刺激激活的脑结构。在目前97%的人群(CC97=22 mA)发生癫痫所需的强度下，6赫兹发作没有区分所测试的AEDs的临床类别。电流强度增加50%(即32 mA)会降低6赫兹发作对苯妥英钠和拉莫三嗪的敏感性。在电流强度为2×CC97(即44 mA)时，只有左乙拉西坦和丙戊酸两种抗癫痫药对6赫兹惊厥表现出完全保护作用，尽管与低刺激强度相比，这两种药物的药效有所降低。22 mA和32 mA刺激强度诱发的6赫兹惊厥的c-Fos染色仍局限于杏仁核和梨状皮质。将刺激强度增加到44 mA会导致齿状回额外的浓染。这种齿状回的恢复可能是44 mA时左乙拉西坦和丙戊酸药效下降的原因。药理学结果结合c-Fos免疫组织化学结果提示，6 Hz刺激可能为治疗难治性边缘癫痫提供了一种有用的模型。(C)2001年，爱思唯尔科学公司出版。
Originally described as a model of 'psychomotor seizures' (J. Pharmacol. Exp. Ther. (1953) 107-273), the 6, Hz corneal stimulation model was abandoned shortly after its description because of its lack of sensitivity to phenytoin. This observation is the basis for the present study designed to validate the 6 Hz seizure as a model, of therapy-resistant epilepsy. The pharmacological profile of the 6 Hz seizure was determined at varying current intensities using seven established AEDs (phenytoin, carbamazepine, clonazepam, phenobarbital, ethosuximide, trimethadione, valproic acid) and five second-generation AEDs (lamotrigine, levetiracetam, felbamate, tiagabine, topiramate). The immediate early gene c-Fos was used as a marker of seizure-induced neuronal activation to help define those brain structures that were activated by 6 Hz corneal stimulation. At the current intensity required to produce a seizure in 97% of the population (CC97 = 22 mA), the 6 Hz seizure did not discriminate between clinical classes of AEDs tested. Increasing the current intensity by 50% (i.e. 32 mA) decreased the sensitivity of the 6 Hz seizure to phenytoin and lamotrigine. At a current intensity of 2 x CC97 (i.e. 44 mA), only two AEDs, levetiracetam and valproic acid, displayed complete protection against the 6 Hz seizure, though the efficacy of these drugs was reduced when compared to the lower stimulation intensities. Intense c-Fos staining from 6 Hz seizures induced by 22 and 32 mA stimulus intensities remained localized to the amygdala and piriform cortex. Increasing the stimulus intensity to 44 mA resulted in additional heavy staining of the dentate gyrus. This recruitment of the dentate gyrus may account for the decrease in potency of levetiracetam and valproic acid at 44 mA. The pharmacological results combined with the c-Fos immunohistochemistry suggest that the 6 Hz stimulation may provide a useful model of therapy-resistant limbic seizures. (C) 2001 Published by Elsevier Science B.V.