Therapeutic doses of topiramate are not toxic to the developing rat brain
Therapeutic doses of topiramate are not toxic to the developing rat brain
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DOI：
10.1016/j.expneurol.2004.01.025
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
Ikonomidou, C
中科院分区：
文献类型：
--
作者：
Glier, C;Dzietko, M;Ikonomidou, C
用于治疗孕妇、婴儿和幼儿癫痫发作的抗癫痫药物（AEDs）可能会导致认知障碍。其中一个涉及的机制是增强凋亡神经元死亡，这发生在发育中的大脑生理。我们研究了一种新的抗癫痫药物托吡酯是否在发育中的大鼠大脑中具有神经毒性。50 mg/kg及以上剂量的托吡酯可轻微但显著地促进7日龄大鼠脑中凋亡神经元的死亡。这些剂量比对托吡酯有反应的幼鼠癫痫模型中报道的ED50剂量高几倍。电子显微镜证实，托吡酯处理后死亡的神经元与发育过程中发生生理性细胞死亡的神经元表现出相同的形态学特征。与苯妥英、丙戊酸和苯巴比妥的神经毒性相比，托吡酯的有效抗惊厥剂量和神经毒性剂量之间的分离更大，神经毒性作用更低。(C) 2004爱思唯尔公司版权所有。
Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment. One of the implicated mechanisms is enhancement of apoptotic neuronal death, which occurs physiologically in the developing brain. We investigated whether topiramate, one of the newer antiepileptic drugs, has neurotoxic properties in the developing rat brain. Topiramate slightly but significantly enhanced apoptotic neuronal death in the 7-day-old rat brain at doses of 50 mg/kg and above. These doses are several folds higher than reported ED50 doses in infant rodent seizure models that respond to topiramate. Electron microscopy confirmed that dying neurons following topiramate treatment displayed the same morphological features as neurons undergoing physiological cell death during development. When compared to the neurotoxicity profile of phenytoin, valproate, and phenobarbital, the separation between the effective anticonvulsant dose and the neurotoxic dose was greater for topiramate and the neurotoxic effect was lower. (C) 2004 Elsevier Inc. All rights reserved.