Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
Epilepsy Res. 2010 Sep;91(1):49-56. doi: 10.1016/j.eplepsyres.2010.06.011.
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).
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.
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.
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.
癫痫持续状态（SE）导致促炎蛋白（包括环氧化酶-2（cox-2））上调，这可能与致痫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期间调节 P-糖蛋白（P-gp）的表达。P-gp 可通过减少苯妥英（PHT）等抗癫痫药物进入大脑而导致药物抵抗。在这里，我们研究了 cox-2 抑制对颞叶癫痫（TLE）大鼠模型中癫痫发生、自发性癫痫发作和 PHT 治疗的影响。
在电诱导 SE 前 1 天开始用 cox-2 抑制剂 SC-58236（SC）进行 3 天治疗。慢性癫痫大鼠用 SC 治疗 14 天，随后进行 7 天 SC/PHT 联合治疗。使用脑电图连续监测癫痫发作活动。
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%的大鼠在治疗的第 2 周内癫痫发作次数增加。SC/PHT 治疗仅在 2 天内显著减少癫痫发作。
SE 前开始的 SC 治疗和慢性癫痫大鼠的 14 天治疗都在 TLE 大鼠模型中产生了不良影响。尽管 SC/PHT 治疗暂时降低了癫痫发作频率，但 SC 似乎不适合作为抗癫痫发生或抗癫痫治疗的方法。
