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

Neurobiol Dis. 2006 Aug;23(2):237-46. doi: 10.1016/j.nbd.2006.02.016. Epub 2006 Jun 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Celecoxib
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hippocampus / physiopathology*
  • Male
  • Muscarinic Agonists
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology*
  • Pilocarpine
  • Pyrazoles / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Status Epilepticus / chemically induced
  • Status Epilepticus / drug therapy*
  • Sulfonamides / therapeutic use*


  • Cyclooxygenase Inhibitors
  • Muscarinic Agonists
  • Pyrazoles
  • Sulfonamides
  • Pilocarpine
  • Celecoxib