The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy
The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy
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DOI：
10.1016/j.expneurol.2010.03.014
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发表时间：
2010-07-01
影响因子：
5.3
通讯作者：
Loescher, Wolfgang
中科院分区：
文献类型：
--
作者：
Polascheck, Nadine;Bankstahl, Marion;Loescher, Wolfgang
环氧化酶-2 (COX-2)，催化促炎前列腺素的产生，在各种损伤后在大脑中被诱导，从而促进脑炎症过程，参与这些损伤的长期后果。越来越多的证据支持炎症可能有助于脑损伤后癫痫发生和神经元损伤的发展。因此，抗炎治疗，如选择性COX-2抑制剂，可能构成脑损伤（如头部创伤、脑缺血或癫痫持续状态（SE））后抗癫痫发生或疾病改善的新途径。然而，在最近的大鼠实验中，SE后预防性给予两种不同的COX-2抑制剂，结果相互矛盾。在本研究中，我们评估了parcoxib（一种高效选择性COX-2抑制剂valdecoxib的前药）治疗是否能改变匹罗卡品诱导的大鼠SE的长期后果。服用帕瑞昔布，每日两次，剂量为10 mg/kg，持续18天。治疗结束后5周，通过连续视频/脑电图监测记录自发性复发性癫痫发作。用帕瑞昔布进行预防性治疗，可防止se诱导的前列腺素E-2升高，减轻海马和梨状皮质的神经元损伤。然而，癫痫发作后自发性发作的发生率、频率或持续时间或与癫痫相关的行为和认知改变不受帕瑞昔布的影响。只有自发性癫痫发作的严重程度有所降低，表明有改善疾病的作用。这些结果证实COX-2有助于SE后神经元损伤的发生，但抑制COX-2并不是改变癫痫发生的有效手段。(C) 2010爱思唯尔公司版权所有。
The enzyme cyclooxygenase-2 (COX-2), which catalyzes the production of pro-inflammatory prostaglandins, is induced in the brain after various insults, thus contributing to brain inflammatory processes involved in the long-term consequences of such insults. Mounting evidence supports that inflammation may contribute to epileptogenesis and neuronal injury developing after brain insults. Anti-inflammatory treatments, such as selective COX-2 inhibitors, may thus constitute a novel approach for anti-epileptogenesis or disease-modification after brain injuries such as head trauma, cerebral ischemia or status epilepticus (SE). However, recent rat experiments with prophylactic administration of two different COX-2 inhibitors after SE resulted in conflicting results. In the present study, we evaluated whether treatment with parecoxib, a pro-drug of the highly potent and selective COX-2 inhibitor valdecoxib, alters the long-term consequences of a pilocarpine-induced SE in rats. Parecoxib was administered twice daily at 10 mg/kg for 18 days following SE. Five weeks after termination of treatment, spontaneous recurrent seizures were recorded by continuous video/EEG monitoring. Prophylactic treatment with parecoxib prevented the SE-induced increase in prostaglandin E-2 and reduced neuronal damage in the hippocampus and piriform cortex. However, the incidence, frequency or duration of spontaneous seizures developing after SE or the behavioral and cognitive alterations associated with epilepsy were not affected by parecoxib. Only the severity of spontaneous seizures was reduced, indicating a disease-modifying effect. These results substantiate that COX-2 contributes to neuronal injury developing after SE, but inhibition of COX-2 is no effective means to modify epileptogenesis. (C) 2010 Elsevier Inc. All rights reserved.