Effects of lamotrigine and topiramate on hippocampal neurogenesis in experimental temporal-lobe epilepsy
Effects of lamotrigine and topiramate on hippocampal neurogenesis in experimental temporal-lobe epilepsy
复制标题
拉莫三嗪和托吡酯对实验性颞叶癫痫海马神经发生的影响
DOI：
10.1016/j.brainres.2009.12.024
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发表时间：
2010-02-08
期刊：
影响因子：
2.9
通讯作者：
Jiang, Wen
中科院分区：
文献类型：
--
作者：
Chen, Jing;Quan, Qing-Yun;Jiang, Wen
拉莫三嗪（LTG）和托吡酯（TPM）是两种最常用的新一代抗癫痫药物（AEDs），已被证明对癫痫患者无不良反应和认知功能损害。由于癫痫诱导的神经发生可能导致与癫痫持续状态（SE）相关的认知缺陷，我们研究了这两种药物是否对成年大鼠海马中癫痫诱导的神经发生产生不同的影响。采用匹罗卡品锂诱发颞叶癫痫模型。SE后5小时，在整个实验期间每天两次灌胃给予LTG和TPM，每日总剂量分别为20和80 mg/kg。用5-溴脱氧尿苷和双皮质素免疫组化法检测海马神经发生。LTG和TPM处理显著抑制海马神经前体细胞的增殖，但不影响新生细胞的神经元分化。两种抗癫痫药物的长期治疗减少了SE后自发复发性癫痫发作的次数，并减轻了慢性癫痫引起的齿状门神经元损伤。最终，TPM显著增加癫痫发作后齿状回颗粒细胞层中新生神经元的数量，可能是通过促进新生神经元的存活。相反，LTG治疗显著减少癫痫发作后异位肺门新生神经元的数量。它们都不能阻止癫痫海马新生神经元的门基底树突的形成。这些结果表明，TPM而不是LTG促进SE后海马异常神经元再生，这可能部分与其对认知功能的差异性影响有关。(C)2009 Elsevier B. V.保留所有权利。
Lamotrigine (LTG) and topiramate (TPM), two of the most commonly used new-generation antiepileptic drugs (AEDs), have been shown to produce no adverse and impaired cognitive effects in patients with epilepsy, respectively. As seizure-induced neurogenesis might contribute to cognitive deficits that are associated with status epilepticus (SE), we examined whether these two drugs produce differential effects on seizure-induced neurogenesis in the hippocampus of adult rats. Lithium pilocarpine model was used to mimic human temporal-lobe epilepsy. Five hours after SE, LTG and TPM were administered intragastrically twice daily throughout the entire length of the experiment with total daily dose of 20 and 80 mg/kg, respectively. The hippocampal neurogenesis was examined using 5-bromodeoxyuridine and doublecortin immunohistochemistry. Both LTG and TPM treatments significantly inhibited seizure-induced proliferation of neural progenitors in the hippocampus, but did not affect the neuronal differentiation of newborn cells. Longterm treatment with both AEDs decreased the number of spontaneous recurrent seizures after SE and alleviated chronic seizure-induced neuronal injury in the dentate hilus. Eventually, TPM significantly increased the number of newborn neurons in the dentate granular cell layer after seizures likely by promoting the survival of newborn neurons. In contrast, LTG treatment significantly reduced the number of ectopic hilar newborn neurons after seizures. Neither of them prevented the formation of hilar basal dendrites of newborn neurons in the epileptic hippocampus. These results indicate that TPM but not LTG promotes aberrant neuron regeneration in the hippocampus after SE, which might be partially related to their differential effects on cognitive function. (C) 2009 Elsevier B.V. All rights reserved.