Abstract
Focal ischemia was induced in the fronto-parietal region of rat brain, by injection of Rose Bengal, followed by light activation. Focal ischemia was accompanied by formation of PGD(2) peaking 60-90 min post irradiation and declining thereafter. Increased Cycloxygenase-2 (COX-2) expression was also observed. Control ischemic rats showed distinct morphological alterations with necrosis of neurons, glial cells and blood vessels, surrounded by a halo with pyknotic cells with cytoplasm swelling and vacuolization. Compound SC58236, a selective COX-2 inhibitor, dose-dependently prevented, ischemia-induced eicosanoid formation (area under the curve (AUC) of controls: 3.11 +/- 0.87; AUC of 20 mg/kg SC58236: 0.39 +/- 0.24), and caused significant reduction of damaged area (30.7 and 18.9% at SC58236 20 and 6.6 mg/kg), suggesting that selective inhibitors of COX-2 are neuroprotective.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain Ischemia / drug therapy*
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Brain Ischemia / metabolism
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Brain Ischemia / physiopathology
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Cerebral Cortex / drug effects
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Cerebral Cortex / pathology
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Cerebral Cortex / physiopathology
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Fluorescent Dyes / pharmacology
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / metabolism
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Male
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Microdialysis
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Microscopy, Electron
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Necrosis
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Nerve Degeneration / etiology
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Nerve Degeneration / physiopathology
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Nerve Degeneration / prevention & control*
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Neurons / drug effects
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Neurons / pathology
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Neurons / ultrastructure
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Neuroprotective Agents / pharmacology*
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Prostaglandin D2 / antagonists & inhibitors
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Prostaglandin D2 / metabolism
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Prostaglandin-Endoperoxide Synthases / metabolism
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Pyrazoles*
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Rats
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Rats, Wistar
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Rose Bengal / pharmacology
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Sulfonamides*
Substances
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4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Fluorescent Dyes
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Isoenzymes
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Neuroprotective Agents
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Pyrazoles
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Sulfonamides
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Rose Bengal
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Prostaglandin D2