Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
Brain Res. 2010 Feb 8;1313:270-82. doi: 10.1016/j.brainres.2009.12.024. Epub 2009 Dec 16.
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. Long-term 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.
左乙拉西坦（LTG）和托吡酯（TPM）是两种最常用的新一代抗癫痫药物（AEDs），分别已被证明在癫痫患者中不会产生不良和认知障碍的影响。由于癫痫发作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的癫痫发作诱导的神经发生产生不同的影响。使用锂匹鲁卡品模型模拟人类颞叶癫痫。SE 后 5 小时，通过胃内给药每天两次给予 LTG 和 TPM，总日剂量分别为 20 和 80mg/kg，持续整个实验过程。通过 5-溴脱氧尿苷和双皮质素免疫组织化学检测海马神经发生。LTG 和 TPM 治疗均显著抑制 SE 后海马中神经祖细胞的增殖，但不影响新生细胞的神经元分化。长期使用两种 AED 可减少 SE 后的自发性复发发作次数，并减轻慢性 SE 引起的齿状回神经元损伤。最终，TPM 显著增加了 SE 后齿状回颗粒细胞层中新神经元的数量，可能是通过促进新生神经元的存活。相比之下，LTG 治疗后明显减少了 SE 后异常的齿状回新生神经元的数量。它们都没有阻止癫痫海马中新神经元的齿状回基底树突的形成。这些结果表明，TPM 而不是 LTG 促进 SE 后海马中异常的神经元再生，这可能与它们对认知功能的不同影响部分相关。
