PMID- 15189763
OWN - NLM
STAT- MEDLINE
DCOM- 20050228
LR  - 20161124
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 493
IP  - 1-3
DP  - 2004 Jun 16
TI  - Opposing effects of cyclooxygenase-2 selective inhibitors on oxygen-glucose 
      deprivation-induced neurotoxicity.
PG  - 45-55
AB  - Cyclooxygenase-2 inhibitors protect against excitotoxicity in vitro yet provide 
      conflicting results in in vivo models of ischemia. To bridge the gap in 
      understanding the discrepancies among these studies, the effects of different 
      cyclooxygenase-2 inhibitors were studied in an in vitro model of ischemia. 
      Oxygen-glucose deprivation (OGD) induced cyclooxygenase-2 protein expression in 
      neuronal cortical cultures. Cyclooxygenase-2 inhibitors exhibited opposing 
      effects on neuronal death induced by OGD. The acidic sulfonamides, 
      N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) and 
      N-(4-nitro-2-phenoxyphenyl)-methanesulfonamide (nimesulide), aggravated neuronal 
      death by enhancing OGD-induced increases in extracellular glutamate and 
      intracellular Ca2+ levels. In contrast, 
      1-[(4-methylsulfonyl)phenyl]-3-tri-fluoromethyl-5-(4-fluorophenyl)pyrazole 
      (SC-58125) dose-dependently protected cultures against OGD by suppressing 
      increases in extracellular glutamate and intracellular Ca2+ levels. The 
      NS-398-induced aggravation of neuronal death was lost if the inhibitor was added 
      only following the OGD. The timing of inhibitor application also determined its 
      effects on N-methyl-D-aspartate (NMDA)-induced excitoxicity. NS-398 was 
      protective when added both during and post-NMDA exposure, but not if NS-398 was 
      also applied for 60 min prior to the insult. In contrast, SC-58125 afforded 
      protection against NMDA in the presence or absence of a pre-incubation period. 
      This study demonstrates that certain cyclooxygenase-2 inhibitors have opposing 
      effects on neuronal survival depending on the timing of application and the 
      nature of the insult. These results may account for the discrepancies among 
      previous studies which used different inhibitors and different models of 
      neurotoxicity.
CI  - Copyright 2004 Elsevier B.V.
FAU - Gendron, Tania F
AU  - Gendron TF
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, 
      Canada K1H 8M5. tania.gendron@nrc-cnrc.gc.ca
FAU - Brunette, Eric
AU  - Brunette E
FAU - Mealing, Geoffrey A R
AU  - Mealing GA
FAU - Nguyen, Adele
AU  - Nguyen A
FAU - Tauskela, Joseph S
AU  - Tauskela JS
FAU - Morley, Paul
AU  - Morley P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Glutamates)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Sulfonamides)
RN  - 123653-11-2 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide)
RN  - 162054-19-5 
      (1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - SY7Q814VUP (Calcium)
RN  - V4TKW1454M (nimesulide)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Canada
MH  - Cell Death/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/embryology/metabolism
MH  - Cyclooxygenase 2
MH  - Cyclooxygenase 2 Inhibitors
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Cytosol/drug effects/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Enzyme Induction/drug effects/genetics
MH  - Extracellular Space/chemistry/drug effects/metabolism
MH  - Glucose Metabolism Disorders/*complications/metabolism/prevention & control
MH  - Glutamates/chemistry/drug effects/metabolism
MH  - Hypoxia/*complications/metabolism/prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurotoxicity Syndromes/*etiology/metabolism
MH  - Nitrobenzenes/antagonists & inhibitors/pharmacology
MH  - Prostaglandin-Endoperoxide Synthases/genetics/metabolism
MH  - Pyrazoles/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/drug effects/physiology
MH  - Sulfonamides/antagonists & inhibitors/pharmacology
MH  - Time Factors
EDAT- 2004/06/11 05:00
MHDA- 2005/03/01 09:00
CRDT- 2004/06/11 05:00
PHST- 2004/04/15 00:00 [received]
PHST- 2004/04/20 00:00 [accepted]
PHST- 2004/06/11 05:00 [pubmed]
PHST- 2005/03/01 09:00 [medline]
PHST- 2004/06/11 05:00 [entrez]
AID - S001429990400411X [pii]
AID - 10.1016/j.ejphar.2004.04.026 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2004 Jun 16;493(1-3):45-55. doi: 10.1016/j.ejphar.2004.04.026.