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Cyclooxygenase-2 selective inhibitors aggravate kainic acid induced seizure and neuronal cell death in the hippocampus.

Authors
Baik, EJ; Kim, EJ; Lee, SH; Moon, C
Citation
Brain research, 843(1-2):118-129, 1999
Journal Title
Brain research
ISSN
0006-89931872-6240
Abstract
Cyclooxygenase-2 (COX-2) in the brain is expressed constitutively and also increased in pathological conditions such as seizure, cerebral ischemia, and inflammation. This study examined the role of COX-2 in kainic acid-induced seizure and in the following neuronal death by using selective inhibitors. Systemic kainate injection (50 mg/kg; i.p.) in mice evoked seizure within 15 min and led to 29% mortality within 2 h. TUNEL-positive neuronal death peaked at 3 days after injection and was prominent in CA(3a) regions of the hippocampus. NS-398 or celecoxib (10 mg/kg, COX-2 selective inhibitor) and indomethacin (5 mg/kg, nonselective inhibitor) exaggerated kainic acid-induced seizure activity and mortality. COX-2 selective inhibitors induced the seizure at earlier onset and more severe mortality within the first hour than indomethacin and aspirin. NS-398 also aggravated kainic acid-induced TUNEL positive neuronal death and decreased Cresyl violet stained viable neurons, and extended lesions to CA(1) and CA(3b). Kainic acid increased the levels of PGD(2), PGF(2a) and PG E(2) in the hippocampus immediately after injection. Indomethacin attenuated the production of basal and kainic acid-induced prostaglandins. In contrast, NS-398 failed to reduce until the first 30 min after kainic acid injection, during which the animals were severely seizured. It has been challenged the endogenous PGs might have anticonvulsant properties. Thus, COX-2 selective inhibitor, including nonselective inhibitor such as indomethacin, aggravated kainic acid-induced seizure activity and the following hippocampal neuronal death even with variable prostaglandin levels.
MeSH terms
AnimalsAspirin/toxicityCell Death/drug effectsCyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase Inhibitors/toxicity*Drug SynergismHippocampus/drug effectsHippocampus/pathology*Indomethacin/toxicityIsoenzymes/metabolism*Kainic Acid/toxicity*MaleMiceNeurons/drug effectsNeurons/pathology*Nitrobenzenes/toxicityProstaglandin-Endoperoxide Synthases/metabolism*Seizures/chemically induced*Seizures/pathologySeizures/physiopathology*Sulfonamides/toxicityTime Factors
PMID
10528118
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
백, 은주김, 은주이, 수환문, 창현
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