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 tissue. The purpose of this study was to examine the efficacy of compounds that quench free radicals in improving the outcome in rats with experimental intracerebral hemorrhage. Intracerebral hemorrhage was induced 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-phenyl-N-tert-butyl nitrone starting 2 h after hemorrhage, with treatment continued for 10 days after induction of hemorrhage. Outcome was assessed by behavioral analyses, magnetic resonance imaging, and histopathology. A trend towards behavioral improvement was found for rats treated with alpha-tocopherol/ascorbic acid, while behavior was significantly improved following intracerebral hemorrhage in rats treated with dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone. These results suggest that free radicals may play a role in the development of brain injury following intracerebral hemorrhage, and that compounds that interrupt the free radical cascade may improve outcome. However, treatment did not significantly affect edema, resolution of the hematoma, or neuronal injury in tissue adjacent to the hemorrhage.
Peeling
J
J
Department of Radiology, The University of Manitoba, Winnipeg, Manitoba, Canada. jpeeling@ms.umanitoba.ca
Yan
H J
HJ
Chen
S G
SG
Campbell
M
M
Del Bigio
M R
MR
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000378:metabolism*; D003497:Cyclic N-Oxides; D005247:Feeding Behavior; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D014810:Vitamin E; C029217:phenyl-N-tert-butylnitrone; C038983:1,3-dimethylthiourea; D013890:Thiourea; D001205:Ascorbic Acid