Early postnatal exposure of rats to lamotrigine, but not phenytoin, reduces seizure threshold in adulthood.
Early postnatal exposure of rats to lamotrigine, but not phenytoin, reduces seizure threshold in adulthood.
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DOI：
10.1111/j.1528-1167.2010.02971.x
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发表时间：
2011-04
期刊：
影响因子：
5.6
通讯作者：
Kondratyev A
中科院分区：
文献类型：
--
作者：
Forcelli PA;Gale K;Kondratyev A
鉴于以往的报告中的变化癫痫发作的敏感性成年大鼠暴露于苯巴比妥或地西泮作为幼崽，我们研究了早期生活暴露于拉莫三嗪和苯妥英钠，两种常用的抗癫痫药物（AED），其对癫痫发作阈值的影响在成年大鼠。我们发现，在出生后第二周暴露于拉莫三嗪6天的幼鼠，在成年后进行测试时，戊四氮诱发癫痫发作的阈值明显较低。相反，出生后第二周苯妥英暴露对成人癫痫发作阈值没有显著影响。在所有测试组中，阈值时的癫痫发作评分相当。我们研究中使用的拉莫三嗪剂量（20 mg/kg）低于引起发育神经元凋亡所需的剂量，而使用的苯妥英剂量（50 mg/kg）高于发育神经毒性所需的剂量。因此，我们的研究结果表明，癫痫易感性的神经发育改变可能通过独立于神经损伤或致畸的机制发生。我们的研究结果支持在怀孕或婴儿期使用某些AED治疗可能会改变以后生活中癫痫发作的易感性，在检查导致成年期癫痫发作易感性的早期生活因素时应考虑这种可能性。
In view of previous reports of changes in seizure susceptibility in adult rats exposed to phenobarbital or diazepam as pups, we examined the effects of early-life exposure to lamotrigine and phenytoin, two commonly used antiepileptic drugs (AEDs), for their effect on seizure threshold in adult rats. We found that pups exposed to lamotrigine for six days during the second postnatal week had a significantly lower threshold for pentylenetetrazol-evoked seizures when tested as adults. In contrast, phenytoin exposure during the second postnatal week was without a significant effect on seizure threshold in adults. Seizure scores at threshold were comparable across all groups tested. The dose of lamotrigine used in our study (20 mg/kg) was below that required to cause developmental neuronal apoptosis, while the dose of phenytoin used (50 mg/kg) was above that required for developmental neurotoxicity. Thus, our findings suggest that neurodevelopmental alterations in seizure susceptibility may occur via mechanisms that are independent of those responsible for neural injury or teratogenesis. Our findings support the possibility that therapy with certain AEDs during pregnancy or infancy may alter seizure susceptibility later in life, a possibility that should be taken into account when examining early-life factors that contribute to seizure susceptibility in adulthood.
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影响因子：
3.3
作者：
Ornoy, Asher
通讯作者：
Ornoy, Asher
影响因子：
2.9
作者：
Tsenov, Grygoryi;Redkozubova, Olga;Mares, Pavel
通讯作者：
Mares, Pavel
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J
DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ
DOI：
10.1124/jpet.107.123133
发表时间：
2007-08-01
影响因子：
3.5
作者：
Katz, Irina;Kim, Jinsook;Kondratyev, Alexei
通讯作者：
Kondratyev, Alexei