Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus
Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus
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DOI：
10.1016/j.nbd.2006.02.016
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发表时间：
2006-08-01
影响因子：
6.1
通讯作者：
Roh, Jae-Kyu
中科院分区：
文献类型：
--
作者：
Jung, Keun-Hwa;Chu, Kon;Roh, Jae-Kyu
最近的证据表明，异常的神经发生和星形胶质细胞在癫痫的发病机制中起着关键作用。干细胞微环境的改变，如小胶质细胞的激活和环氧合酶-2的诱导，可能会导致异位神经发生或星形胶质细胞增生症。在这里，我们研究了选择性环氧合酶-2抑制剂塞来昔布的炎性阻断是否可以调节癫痫大鼠大脑微环境的改变。塞来昔布可降低匹罗卡品诱导的长时间癫痫发作后出现自发性反复发作的可能性。在潜伏期内，塞来昔布可阻止门区和CA1区神经元死亡和小胶质细胞活化，并抑制门区异位颗粒细胞和CA1区新胶质细胞的产生。在人神经干细胞培养中进一步证实了塞来昔布对前体细胞的直接抑制作用。这些发现提供了COX-2诱导在癫痫发生中起重要作用的证据，并提示COX-2抑制剂在慢性癫痫中的潜在治疗作用。(C)2006 Elsevier Inc.保留所有权利。
Recent evidences suggest key roles of abnormal neurogenesis and astrogliosis in the pathogenesis of epilepsy. Alterations in the microenvironment of the stem cell, such as microglial activation and cyclooxygenase-2 induction may cause ectopic neurogenesis or astrogliosis. Here, we examined if inflammatory blockade with celecoxib, a selective cyclooxygenase-2 inhibitor, could modulate the altered microenvironment in the epileptic rat brain. Celecoxib attenuated the likelihood of developing spontaneous recurrent seizures after pilocarpine-induced prolonged seizure. During the latent period, celecoxib prevented neuronal death and microglia activation in the hilus and CA1 and inhibited the generation of ectopic granule cells in the hilus and new glia in CA1. The direct inhibition of precursor cells by celecoxib was further demonstrated in human neural stem cells culture. These findings raise the evidence of COX-2 induction to act importantly on epileptogenesis and suggest a potential therapeutic role for COX-2 inhibitors in chronic epilepsy. (c) 2006 Elsevier Inc. All rights reserved.