Efficacy of disodium 4-[( tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke

Because free radical mechanisms may contribute to brain injury in hemorrhagic stroke, the effect of the free radical trapping agent disodium 4-[( tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) was investigated on outcome following intracerebral hemorrhage (ICH) in rat. ICH was indu...

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Bibliographic Details
Published in:Neuropharmacology 2001-03, Vol.40 (3), p.433-439
Main Authors: Peeling, James, Del Bigio, Marc R, Corbett, Dale, Green, A.Richard, Jackson, David M
Format: Article
Language:English
Subjects:
Animals
Behavior
Behavior, Animal - drug effects
Benzenesulfonates
Biological and medical sciences
Blood Cell Count
Body Weight - drug effects
Brain - drug effects
Brain - immunology
Brain - pathology
Cell Death - drug effects
Cerebral Hemorrhage - complications
Cerebral Hemorrhage - diagnosis
Cerebral Hemorrhage - drug therapy
Disease Models, Animal
Free Radical Scavengers - administration & dosage
Free radicals
Hematoma - immunology
Hematoma - pathology
Inflammation
Infusion Pumps
Injections, Subcutaneous
Intracerebral hemorrhage
Magnetic Resonance Imaging
Male
Medical sciences
Miscellaneous
Motor Skills - drug effects
MR imaging
Neuropharmacology
Neuroprotective Agents - administration & dosage
Neutrophil Infiltration - drug effects
Neutrophil Infiltration - immunology
Nitrogen Oxides - administration & dosage
Nitrogen Oxides - pharmacokinetics
NXY-059
Pharmacology. Drug treatments
Pilot Projects
Rats
Rats, Sprague-Dawley
Stroke - drug therapy
Stroke - etiology
Stroke - metabolism
Treatment Outcome
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Summary:Because free radical mechanisms may contribute to brain injury in hemorrhagic stroke, the effect of the free radical trapping agent disodium 4-[( tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) was investigated on outcome following intracerebral hemorrhage (ICH) in rat. ICH was induced in 20 adult rats by infusion of collagenase into the caudate-putamen. Thirty minutes later rats were treated with NXY-059 (50 mg/kg subcutaneous plus 8.8 mg/kg/h for 3 days subcutaneous delivered via implanted osmotic pumps) or saline (equivalent volumes). Magnetic resonance imaging 24 h after ICH confirmed that the hemorrhage was uniform in the two groups, and subsequent imaging at 7 and 42 days post-ICH showed that the hematoma resolved similarly in the two groups. Behavioral testing on days 1, 3, 7, 14, and 21 after ICH showed that rats treated with NXY-059 had significantly decreased neurological impairment at all times. Deficits in skilled forelimb use 4–5 weeks post-ICH, and in striatal function 6 weeks post-ICH, were not reduced by treatment with NXY-059. Treatment with NXY-059 significantly reduced the neutrophil infiltrate observed 48 h post-hemorrhage in the vicinity of the hematoma, and the number of TUNEL-positive cells 48 h post-hemorrhage at the hematoma margin. However, by 6 weeks there were no differences in neuronal densities in treated and control rats.
ISSN:0028-3908
1873-7064
DOI:10.1016/S0028-3908(00)00170-2