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Nitroxides are antioxidants that are known to protect cells from oxidative damage. Polynitroxyl albumin (PNA) is a compound of human serum albumin covalently labeled with nitroxides that exhibits a prolonged half-life and an enhanced antioxidant activity. Adult male Sprague–Dawley rats were subjected to 90 min intraluminal middle cerebral artery occlusion and the drug was administered intravenously immediately or 2 h after reperfusion. The effects of the drug were evaluated 24 h after reperfusion. Infarct volume was significantly reduced in immediate (79% reduction) and delayed (53% reduction) PNA-treated groups. The efficacy of a single, delayed i.v. injection of PNA suggests that PNA has great promise in the treatment of acute human stroke.