The Cycloxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of focal ischemia in the rat.

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.

• Authors: S Govoni, E Masoero, L Favalli, A Rozza, R Scelsi, S Viappiani, C Buccellati, A Sala, G Folco
• Journal: Neuroscience letters (Neurosci Lett) Vol. 303 Issue 2 Pg. 91-4 (May 04 2001) ISSN: 0304-3940 [Print] Ireland
• PMID: 11311500 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Fluorescent Dyes
• Isoenzymes
• Neuroprotective Agents
• Pyrazoles
• Sulfonamides
• Rose Bengal
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Prostaglandin D2

Topics

• Animals
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Cerebral Cortex (drug effects, pathology, physiopathology)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fluorescent Dyes (pharmacology)
• Isoenzymes (antagonists & inhibitors, metabolism)
• Male
• Microdialysis
• Microscopy, Electron
• Necrosis
• Nerve Degeneration (etiology, physiopathology, prevention & control)
• Neurons (drug effects, pathology, ultrastructure)
• Neuroprotective Agents (pharmacology)
• Prostaglandin D2 (antagonists & inhibitors, metabolism)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Pyrazoles
• Rats
• Rats, Wistar
• Rose Bengal (pharmacology)
• Sulfonamides