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

• Published in: Neuroscience letters Vol. 303; no. 2; pp. 91 - 94
• Main Authors: Govoni, Stefano, Masoero, Elisabetta, Favalli, Luigia, Rozza, Annalinda, Scelsi, Roberto, Viappiani, Serena, Buccellati, Carola, Sala, Angelo, Folco, Giancarlo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 04.05.2001; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Cerebral Cortex - drug effects; Cerebral Cortex - pathology; Cerebral Cortex - physiopathology; Cerebral ischemia; Cyclooxygenase; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Fluorescent Dyes - pharmacology; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Male; Medical sciences; Microdialysis; Microscopy, Electron; Necrosis; Nerve Degeneration - etiology; Nerve Degeneration - physiopathology; Nerve Degeneration - prevention & control; Neurons - drug effects; Neurons - pathology; Neurons - ultrastructure; Neuropharmacology; Neuroprotection; Neuroprotective agent; Neuroprotective Agents - pharmacology; Pharmacology. Drug treatments; Prostaglandin D2 - antagonists & inhibitors; Prostaglandin D2 - metabolism; Prostaglandin endoperoxide synthase; Prostaglandin-Endoperoxide Synthases - metabolism; Pyrazoles; Rats; Rats, Wistar; Rose Bengal - pharmacology; Sulfonamides; Rats; Neuroprotection; Cerebral ischemia; Cyclooxygenase; Prostaglandin endoperoxide synthase; Animal model; Prostaglandin-endoperoxide synthase; Nervous system diseases; Rat; Enzyme; Rodentia; Enzyme inhibitor; Cardiovascular disease; Neuroprotective agent; Cerebral disorder; Vascular disease; Vertebrata; Mammalia; Ischemia; Central nervous system disease; Oxidoreductases; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)01675-5

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.