Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy
Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy
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DOI：
10.1016/j.eplepsyres.2008.12.006
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发表时间：
2009-03-01
影响因子：
2.2
通讯作者：
Gorter, J. A.
中科院分区：
文献类型：
--
作者：
Holtman, L.;van Vliet, E. A.;Gorter, J. A.
炎症是癫痫持续状态后激活的重要生物学过程，可能与癫痫的发展有关。在这里，我们测试了选择性COX-2抑制剂（SC58236）的抗炎治疗是否可以预防癫痫的发展或改变慢性癫痫阶段的癫痫发作活动。在电诱导SE后4 h开始，在潜伏期内口服SC 58236（10 mg/kg），持续7天。使用EEG/视频监测监测癫痫发作，直至SE后35天。使用免疫细胞化学（NeuN和Ox-42）研究细胞死亡和炎症。当大鼠慢性癫痫时，在1周后和4 - 5个月后使用Timm染色研究发芽。还在慢性癫痫大鼠中给予SC58236 5天。在治疗前、治疗中和治疗后连续监测海马EEG发作。SC58236有效地减少了PGE（2）的产生，但没有改变癫痫发作的发展或海马体中细胞死亡或小胶质细胞活化的程度。在慢性癫痫大鼠中，SC 58236治疗未显示出癫痫发作持续时间或每日癫痫发作频率的任何显著变化。cox-2抑制可有效降低前列腺素水平，但不会改变癫痫发生或慢性癫痫发作活动，这一事实表明，这种类型的治疗（SE后开始）不会提供有效的抗癫痫或抗癫痫治疗。(C)2008 Elsevier B.V.保留所有权利。
Inflammation is an important biological process that is activated after status epilepticus and could be implicated in the development of epilepsy. Here we tested whether an anti-inflammatory treatment with a selective cox-2 inhibitor (SC58236) could prevent the development of epilepsy or modify seizure activity during the chronic epileptic phase. SC58236 was orally administered (10mg/kg) during the latent period for 7 days, starting 4h after electrically induced SE. Seizures were monitored using EEG/video monitoring until 35 days after SE. Cell death and inflammation were investigated using immunocytochemistry (NeuN and Ox-42). Sprouting was studied using Timm's staining after 1 week and after 4-5 months when rats were chronic epileptic. SC58236 was also administered during 5 days in chronic epileptic rats. Hippocampal EEG seizures were continuously monitored before, during and after treatment. SC58236 effectively reduced PGE(2) production but did not modify seizure development or the extent of cell death or microglia activation in the hippocampus. SC58236 treatment in chronic epileptic rats did not show any significant change in seizure duration or frequency of daily seizures. The fact that cox-2 inhibition, which effectively reduced prostaglandin levels, did not modify epileptogenesis or chronic seizure activity suggests that this type of treatment (starting after SE) will not provide an effective anti-epileptogenic or anti-epileptic therapy. (C) 2008 Elsevier B.V. All rights reserved.