Cyclooxygenase-2 inhibitor, celecoxib, inhibits the altered hippocampal neurogenesis with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus.
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.
Jung
Keun-Hwa
KH
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.
Chu
Kon
K
Lee
Soon-Tae
ST
Kim
Juhyun
J
Sinn
Dong-In
DI
Kim
Jeong-Min
JM
Park
Dong-Kyu
DK
Lee
Jung-Ju
JJ
Kim
Seung U
SU
Kim
Manho
M
Lee
Sang Kun
SK
Roh
Jae-Kyu
JK
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*
D016861:Cyclooxygenase Inhibitors; D018721:Muscarinic Agonists; D011720:Pyrazoles; D013449:Sulfonamides; D010862:Pilocarpine; D000068579:Celecoxib