The Cycloxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of focal ischemia in the rat.
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.
Govoni
S
S
Department of Applied and Experimental Pharmacology, University of Pavia, Viale Taramelli 14, 27100, Pavia, Italy. govonis@unipv.it
Masoero
E
E
Favalli
L
L
Rozza
A
A
Scelsi
R
R
Viappiani
S
S
Buccellati
C
C
Sala
A
A
Folco
G
G
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D008854:Microscopy, Electron; D009336:Necrosis; D009410:Nerve Degeneration / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal / Q000494:pharmacology; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005456:Fluorescent Dyes; D007527:Isoenzymes; D018696:Neuroprotective Agents; D015230:Prostaglandin D2; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D012395:Rose Bengal; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides