Document Detail


The selective cyclooxygenase-2 inhibitor rofecoxib reduces kainate-induced cell death in the rat hippocampus.
MedLine Citation:
PMID:  11168565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment of male Sprague-Dawley rats with kainic acid (10 mg/kg, i.p.) triggered limbic seizures in 60% of the animals starting within 30 min and lasting for about 6 h. Cyclooxygenase-2 (COX-2) mRNA was strongly induced in the pyramidal cells of the hippocampus, in the amygdala and the piriform cortex after 8 h, as shown by in situ hybridization, and returned to control levels after 72 h. At this time marked cell loss occurred in the CA1-CA3 areas of the hippocampus. We hypothesize that rofecoxib, a selective COX-2 inhibitor, might abbreviate the late neurotoxicity, possibly associated with COX-2 induction. Animals which developed seizures were treated for 3 days with rofecoxib (10 mg/kg, i.p., n = 12) starting 6 or 8 h after kainic acid injection. Histological staining of viable cells confirmed that rofecoxib treatment selectively diminished cell loss in the hippocampus. The TdT-mediated dUTP nick end labelling (TUNEL) technique was used to estimate delayed cell death. Abundant TUNEL-positive cells were detected in seizure rats 72 h after kainic acid injection in pyramidal cells of the hippocampus (CA1-CA3), in cells of the thalamus, the amygdala and the piriform cortex. Treatment with rofecoxib selectively and significantly (P < 0.05) attenuated the number of TUNEL-positive cells in the hippocampus, whereas the cells of the thalamus, amygdala and piriform cortex were not protected. Therefore we conclude that COX-2 might contribute to cell death of pyramidal cells of the hippocampus as a consequence of limbic seizures.
Authors:
T Kunz; E H Oliw
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The European journal of neuroscience     Volume:  13     ISSN:  0953-816X     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-04-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  569-75     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala Biomedical Centre, PO Box 591, SE-751 24 Uppsala, Sweden. tina.kunz@farmbio.uu.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / drug effects*
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / pharmacology*
Epilepsy / chemically induced,  metabolism
Excitatory Amino Acid Agonists
Gene Expression Regulation, Enzymologic / drug effects
Hippocampus / cytology*,  enzymology*,  physiopathology
In Situ Nick-End Labeling
Isoenzymes / analysis,  antagonists & inhibitors*,  genetics
Kainic Acid
Lactones / pharmacology*
Male
Prostaglandin-Endoperoxide Synthases / analysis,  genetics
Pyramidal Cells / cytology,  drug effects,  enzymology
RNA, Messenger / genetics
Rats
Rats, Sprague-Dawley
Seizures / chemically induced,  metabolism
Sulfones
Chemical
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Cyclooxygenase Inhibitors; 0/Excitatory Amino Acid Agonists; 0/Isoenzymes; 0/Lactones; 0/RNA, Messenger; 0/Sulfones; 0/rofecoxib; 487-79-6/Kainic Acid; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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