title: Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus.
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.
authors.affiliation: Neural Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul, South Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Juhyun
authors.initials: J
authors.lastname: Kim
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Sinn
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.forename: Jung-Ju
authors.initials: JJ
authors.lastname: Lee
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D000818:Animals; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010862:Pilocarpine; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D016861:Cyclooxygenase Inhibitors; D018721:Muscarinic Agonists; D011720:Pyrazoles; D013449:Sulfonamides; D010862:Pilocarpine; D000068579:Celecoxib