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

Keun Hwa Jung, Kon Chu, Soon Tae Lee, Juhyun Kim, Dong In Sinn, Jeong Min Kim, Dong Kyu Park, Jung Ju Lee, Seung U. Kim, Manho Kim, Sang Kun Lee, Jae Kyu Roh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalNeurobiology of Disease
Volume23
Issue number2
DOIs
StatePublished - Aug 2006
Externally publishedYes

Keywords

  • COX-2
  • Celecoxib
  • Ectopic granule cell
  • Epilepsy
  • Epileptogenesis
  • Inflammation
  • Microglia
  • Neurogenesis
  • Spontaneous recurrent seizure

ASJC Scopus subject areas

  • Neurology

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