Literature DB >> 9724811

Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia.

M Nakayama1, K Uchimura, R L Zhu, T Nagayama, M E Rose, R A Stetler, P C Isakson, J Chen, S H Graham.   

Abstract

The inducible isoform of the enzyme cyclooxygenase-2 (COX2) is an immediate early gene induced by synaptic activity in the brain. COX2 activity is an important mediator of inflammation, but it is not known whether COX2 activity is pathogenic in brain. To study the role of COX2 activity in ischemic injury in brain, expression of COX2 mRNA and protein and the effect of treatment with a COX2 inhibitor on neuronal survival in a rat model of global ischemia were determined. Expression of both COX2 mRNA and protein was increased after ischemia in CA1 hippocampal neurons before their death. There was increased survival of CA1 neurons in rats treated with the COX2-selective inhibitor SC58125 [1-[(4-methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl] pyrazole] before or after global ischemia compared with vehicle controls. Furthermore, hippocampal prostaglandin E2 concentrations 24 h after global ischemia were decreased in drug-treated animals compared with vehicle-treated controls. These results suggest that COX2 activity contributes to CA1 neuronal death after global ischemia.

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Year:  1998        PMID: 9724811      PMCID: PMC28002          DOI: 10.1073/pnas.95.18.10954

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  43 in total

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Journal:  Neuron       Date:  1993-08       Impact factor: 17.173

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Journal:  Neurol Res       Date:  1990-12       Impact factor: 2.448

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  91 in total

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4.  SCH58261 the selective adenosine A(2A) receptor blocker modulates ischemia reperfusion injury following bilateral carotid occlusion: role of inflammatory mediators.

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Journal:  Neurochem Res       Date:  2011-11-10       Impact factor: 3.996

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7.  Neuronal cyclooxygenase-2 activity and prostaglandins PGE2, PGD2, and PGF2 alpha exacerbate hypoxic neuronal injury in neuron-enriched primary culture.

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8.  PGE2 EP1 receptor deletion attenuates 6-OHDA-induced Parkinsonism in mice: old switch, new target.

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9.  Selective blockade of PGE2 EP1 receptor protects brain against experimental ischemia and excitotoxicity, and hippocampal slice cultures against oxygen-glucose deprivation.

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