PROTECTIVE EFFECTS OF FREE-RADICAL INHIBITORS IN INTRACEREBRAL HEMORRHAGE IN RAT

Iron compounds formed in the degradation of a hematoma can accelerate the formation of free radicals in adjacent ischemic or hypoperfused ti ssue. The purpose of this study was to examine the efficacy of compoun ds that quench free radicals in improving the outcome in rats with exp erimental intracerebral hemorrhage. Intracerebral hemorrhage was induc ed in rats by injection of bacterial collagenase and heparin into the caudate nucleus. Rats were treated with alpha-tocopherol plus ascorbic acid starting before hemorrhage, or with dimethylthiourea or alpha-ph enyl-N-tert-butyl nitrone starting 2 h after hemorrhage, with treatmen t continued for 10 days after induction of hemorrhage. Outcome was ass essed by behavioral analyses, magnetic resonance imaging, and histopat hology. A trend towards behavioral improvement was found for rats trea ted with alpha-tocopherol/ascorbic acid, while behavior was significan tly improved following intracerebral hemorrhage in rats treated with d imethylthiourea or alpha-phenyl-N-tert-butyl nitrone, These results su ggest that free radicals may play a role in the development of brain i njury following intracerebral hemorrhage, and that compounds that inte rrupt the free radical cascade may improve outcome. However, treatment did not significantly affect edema, resolution of the hematoma, or ne uronal injury in tissue adjacent to the hemorrhage. (C) 1998 Elsevier Science B.V. All rights reserved.