Seizure susceptibility to various convulsant stimuli of knockout interleukin-6 mice
Seizure susceptibility to various convulsant stimuli of knockout interleukin-6 mice
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DOI：
10.1016/j.pbb.2004.01.012
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发表时间：
2004-04-01
影响因子：
3.6
通讯作者：
De Sarro, A
中科院分区：
文献类型：
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作者：
De Sarro, G;Russo, E;De Sarro, A
在本研究中，我们评估了敲除白介素-6 （IL-6(-/-)）小鼠对各种惊厥刺激的敏感性，并与其他三种相关小鼠品系进行了比较。用化学惊厥药物治疗动物，损害γ -氨基丁酸神经传递[戊四唑（PTZ），微毒素，双曲碱，甲基-6,7-二甲氧基-4-乙基- β -羰基-3-羧酸盐（DMCM），甲基- β -羰基-3-羧酸盐（β - ccm）]，增强谷氨酸能神经传递[n -甲基-(D)-天冬氨酸（NMDA）， α -氨基-3-羟基-5-甲基-4-异恶唑丙酸盐（AMPA）和kainic酸（KA）]或K+通道阻滞剂[4-氨基吡啶（4-AP）]。观察惊厥刺激对IL-6（-/-）的行为变化，并与C57、IL-6（+/+）和DBA/2小鼠的行为变化进行比较。对挛性和/或强直性发作的发生率进行评分并进行统计学分析，观察发作易感性可能存在的差异。除DBA/2小鼠外，IL-6（-/-）小鼠对PTZ、β - ccm、DMCM、NMDA、AMPA和KA的发作敏感性显著高于其他小鼠品系。本研究表明，IL-6（-/-）小鼠对某些惊厥刺激的易感性增加。特别是NMDA、AMPA和KA产生的主要惊厥效应表明，IL-6（-/-）小鼠中枢神经系统（CNS）中的兴奋性氨基酸系统更为活跃。提示IL-6（-/-）小鼠可能是一种有效的新型癫痫模型，可用于癫痫发作的病理生理和药理学研究。(C) 2004爱思唯尔公司版权所有。
In the present study, the susceptibility of knockout interleukin-6 (IL-6 (-/-)) mice to various convulsant stimuli has been evaluated and compared with other three related mice strains. Animals were treated with chemical convulsants impairing the gamma-aminobutyric acid neurotransmission [pentylenetetrazole (PTZ), picrotoxin, bicuculline, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), methyl-beta-carbolitie-3-carboxylate (beta-CCM)], enhancing glutamatergic neurotransmission [N-methyl-(D)-aspartate (NMDA), alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainic acid (KA)] or a K+ channel blocker [4-aminopyridine (4-AP)]. The behavioural changes of such convulsant stimuli on IL-6(-/-) were observed and compared with those observed in C57, IL-6(+/+) and DBA/2 mice. The occurrence of clonic and/or tonic seizures was scored and statistically analysed to observe possible differences on seizure susceptibility. The IL-6(-/-) mice exhibited significantly higher seizure susceptibility to PTZ, beta-CCM, DMCM, NMDA, AMPA and KA than did the other mice strains, with the exception of DBA/2 mice. This study, demonstrates that IL-6(-/-) mice possess an increased susceptibility to some convulsant stimuli. In particular, the major convulsant effects produced by NMDA, AMPA and KA suggest that the excitatory amino acid system is more active in the central nervous system (CNS) of IL-6 (-/-) mice. The present data suggest that IL-6(-/-) mice might be a valid novel epileptic model for the study of pathophysiology and pharmacology of epileptic seizures. (C) 2004 Elsevier Inc. All rights reserved.