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Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus

Cited 208 time in Web of Science Cited 217 time in Scopus
Authors
Jung, Keun-Hwa; Chu, Kon; Lee, Soon-Tae; Kim, Juhyun; Sinn, Dong-In; Kim, Jeong-Min; Park, Dong-Kyu; Lee, Jung-Ju; Kim, Seung U.; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu
Issue Date
2006
Publisher
Elsevier
Citation
Neurobiol Dis. 23, 237-246
Keywords
EpileptogenesisCelecoxibEctopic granule cellInflammationCOX-2NeurogenesisMicrogliaSpontaneous recurrent seizureEpilepsy
Abstract
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.
ISSN
0969-9961 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16806953

http://hdl.handle.net/10371/11097
DOI
https://doi.org/10.1016/j.nbd.2006.02.016
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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