Cox-2 inhibition can lead to adverse effects in a rat model for temporal lobe epilepsy
Cox-2 inhibition can lead to adverse effects in a rat model for temporal lobe epilepsy
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DOI：
10.1016/j.eplepsyres.2010.06.011
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发表时间：
2010-09-01
影响因子：
2.2
通讯作者：
Gorter, Jan A.
中科院分区：
文献类型：
--
作者：
Holtman, Linda;van Vliet, Erwin A.;Gorter, Jan A.
目的：癫痫持续状态 (SE) 导致促炎蛋白上调，包括环氧合酶-2 (cox-2)，这可能与癫痫发生过程和癫痫发作有关。最近的研究表明，cox-2可以在癫痫发生和癫痫过程中调节P-糖蛋白（P-gp）的表达。 P-gp 可能通过减少苯妥英 (PHT) 等抗癫痫药物进入大脑而引起耐药性。在这里，我们在颞叶癫痫 (TLE) 大鼠模型中研究了 cox-2 抑制对癫痫发生、自发性癫痫发作和 PHT 治疗的影响。方法：在电诱导 SE 前 1 天开始使用 cox-2 抑制剂 SC-58236 (SC) 进行为期 3 天的治疗。慢性癫痫大鼠接受 SC 治疗 14 天，然后进行为期 7 天的 SC/PHT 联合治疗。使用脑电图连续监测癫痫发作活动。结果：SC 治疗不影响 SE 持续时间，但导致 SE 后前 2 周内死亡的大鼠数量增加。慢性期的 Cox-2 抑制导致 50% 的大鼠在治疗第 2 周癫痫发作次数增加。 SC/PHT 治疗仅持续 2 天即可显着减少癫痫发作。结论：SE 之前开始的 SC 治疗和慢性癫痫大鼠的 14 天治疗均导致 TLE 大鼠模型出现不良反应。尽管 SC/PHT 治疗可暂时降低癫痫发作频率，但 SC 似乎并不是抗癫痫或抗癫痫治疗的合适方法。 (C) 2010 Elsevier B.V. 保留所有权利。
Purpose: Status epilepticus (SE) leads to upregulation of pro-inflammatory proteins including cyclooxygenase-2 (cox-2) which could be implicated in the epileptogenic process and epileptic seizures. Recent studies show that cox-2 can regulate expression of P-glycoprotein (P-gp) during epileptogenesis and epilepsy. P-gp could cause pharmacoresistance by reducing brain entry of anti-epileptic drugs such as phenytoin (PHT). Here we have investigated the effects of cox-2 inhibition on epileptogenesis, spontaneous seizures and PHT treatment in a rat model for temporal lobe epilepsy (TLE).Methods: A 3-day treatment with the cox-2 inhibitor SC-58236 (SC) was started 1 day before electrically induced SE. Chronic epileptic rats were treated with SC for 14 days, which was followed by a 7-day period of SC/PHT combination treatment. Seizure activity was monitored continuously using electroencephalography.Results: SC treatment did not affect SE duration, but led to an increased number of rats that died during the first 2 weeks after SE. Cox-2 inhibition during the chronic period led to an increased number of seizures in the 2nd week of treatment in 50% of the rats. SC/PHT treatment reduced seizures significantly for only 2 days.Conclusions: Both SC treatment that started before SE and the 14-day treatment in chronic epileptic rats led to adverse effects in the TLE rat model. Despite a temporal reduction in seizure frequency with SC/PHT treatment, SC does not seem to be a suitable approach for anti-epileptogenic or anti-epileptic therapy. (C) 2010 Elsevier B.V. All rights reserved.