Cyclooxygenase-2 expression is induced in rat brain after kainate-induced seizures and promotes neuronal death in CA3 hippocampus.
Cyclooxygenase-2 (COX-2) is the predominant isoform of cyclooxygenase in brain. COX-2 activity produces oxidative stress and results in the production of prostaglandins that have many injurious effects. COX-2 transcription is induced by synaptic activity; therefore, COX-2 activity could contribute to epileptic neuronal injury. To address this hypothesis, COX-2 protein expression and PGE2 production were determined after kainate-induced limbic seizures in rats. The effects of a specific COX-2 inhibitor, SC58125, on neuronal survival and PGE2 concentration in the hippocampus were also determined. COX-2 protein expression was increased in CA3, dentate gyrus, and cortex at 18-24 h after seizures. Hippocampal PGE2 levels were increased at 24 h following seizures, and treatment with the selective COX-2 inhibitor SC58125, 3 mg/kg p.o., attenuated the increase in PGE2 concentration. The survival of CA3 neurons at 7 days after seizures was increased in rats treated with SC58125 compared to vehicle controls. There was no effect of drug treatment on body or brain temperature, nor on the duration or rate of Type IV EEG activity. These results suggest that COX-2 activity can contribute to epileptic neuronal injury and that selective COX-2 inhibitors are neuroprotective.
Department of Neurology, University of Pittsburgh, PA 15260, USA.
Kenji
K
Kawaguchi
Robert W
RW
Hickey
Marie E
ME
Rose
Li
L
Zhu
Jun
J
Chen
Steven H
SH
Graham
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018690:Excitatory Amino Acid Agonists; D011720:Pyrazoles; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007608:Kainic Acid