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 i njection of Rose Bengal, followed by light activation. Focal ischemia was a ccompanied by formation of PGD(2) peaking 60-90 min post irradiation and de clining thereafter. Increased Cycloxygenase-2 (COX-2) expression was also o bserved. Control ischemic rats showed distinct morphological alterations wi th necrosis of neurons, glial cells and blood vessels, surrounded by a halo with pyknotic cells with cytoplasm swelling and vacuolization. Compound SC 58236, a selective COX-2 inhibitor, dose-dependently prevented, ischemia-in duced 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 red uction of damaged area (30.7 and 18.9% at SC58236 20 and 6.6 mg/kg), sugges ting that selective inhibitors of COX-2 are neuroprotective. (C) 2001 Elsev ier Science Ireland Ltd. All rights reserved.