Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice
Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice
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DOI：
10.1016/j.seizure.2010.12.006
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发表时间：
2011-04-01
影响因子：
3
通讯作者：
Sharma, Krishna Kishore
中科院分区：
文献类型：
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作者：
Agarwal, Nidhi Bharal;Agarwal, Nitin Kumar;Sharma, Krishna Kishore
癫痫患者中经常观察到认知障碍。已经看到，不仅癫痫，而且抗癫痫药物也损害认知功能。本研究旨在评估三种抗惊厥药，即拉莫三嗪（5 mg/kg，p.o.），奥卡西平（15 mg/kg，p.o.）和托吡酯（10 mg/kg，口服）对戊四唑（PTZ）点燃小鼠认知功能和氧化应激的影响。通过给药PTZ（25 mg/kg，i. p.）每隔一天服用一次，直到5周。认知评估后，点燃的发展。在最后一次PTZ给药后24 h和48 h进行高架十字迷宫（ESTA）和被动回避反应（PAR）测试。完成后的行为测试丙二醛（MDA），谷胱甘肽水平，超氧化物歧化酶和过氧化氢酶的活性进行了测量作为氧化应激的指标。本研究的结果表明，托吡酯（10 mg/kg）给药点燃动物延长转移潜伏期和减少降压潜伏期在tumor和PAR测试，分别。然而，拉莫三嗪和奥卡西平并没有改变这两个参数。托吡酯给药点燃以及非点燃动物已显示MDA增加和谷胱甘肽水平降低。拉莫三嗪和奥卡西平并没有表现出显着的改变，氧化应激参数。结论：长期使用托吡酯会损害实验性癫痫患者的认知功能，而拉莫三嗪和奥卡西平更安全。(C)2010年英国癫痫协会。由爱思唯尔有限公司出版。保留所有权利。
Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5 mg/kg, p.o.), oxcarbazepine (15 mg/kg, p.o.) and topiramate (10 mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25 mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24 h and 48 h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10 mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer. (C) 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.