Abstract | BACKGROUND AND PURPOSE: METHODS: Twelve monkeys were trained and tested on a variety of behavioral tasks used to dissociate and quantify motor and spatial deficits. Five minutes after permanent occlusion of the right middle cerebral artery, monkeys received a 1-mL intravenous infusion of either saline or NXY-059 (28 mg x kg(-1)), and osmotic minipumps, model 2001D, were implanted subcutaneously to provide continuous drug or saline infusion for 48 hours. Drug-filled pumps released NXY-059 at 16 mg x kg(-1) x h(-1). The monkeys were retested 3 and 10 weeks after surgery to assess functional disability. Surgery, behavioral testing, and histology were all done blinded to treatment condition. RESULTS: NXY-059-treated monkeys were significantly better at reaching with their hemiparetic arm than were saline-treated monkeys when retested 3 weeks (P:<0.01) and 10 weeks (P:<0.01) after surgery. Drug treatment also significantly lessened the degree of spatial perceptual neglect (P:<0.01), a debilitating though ameliorating consequence of this infarct. NXY-059 treatment reduced the overall amount of brain damage by >50% of saline-treatment values, with similar levels of protection afforded to both white and gray matter. CONCLUSIONS: This novel drug has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species. These findings provide considerable encouragement for the clinical development of NXY-059.
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Authors | J W Marshall, K J Duffin, A R Green, R M Ridley |
Journal | Stroke
(Stroke)
Vol. 32
Issue 1
Pg. 190-8
(Jan 2001)
ISSN: 1524-4628 [Electronic] United States |
PMID | 11136936
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzenesulfonates
- Free Radical Scavengers
- Neuroprotective Agents
- Nitrogen Oxides
- disufenton sodium
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Topics |
- Analysis of Variance
- Animals
- Arm
(physiopathology)
- Behavior, Animal
(drug effects)
- Benzenesulfonates
- Body Temperature
(drug effects)
- Brain
(drug effects, pathology, physiopathology)
- Brain Ischemia
(drug therapy, etiology, physiopathology)
- Callithrix
- Choice Behavior
(drug effects)
- Disease Models, Animal
- Free Radical Scavengers
(administration & dosage)
- Hemodynamics
(drug effects)
- Infarction, Middle Cerebral Artery
(complications, drug therapy, pathology)
- Infusions, Intravenous
- Kinesis
(drug effects)
- Motor Activity
(drug effects)
- Neuroprotective Agents
(administration & dosage, pharmacokinetics)
- Nitrogen Oxides
(administration & dosage, blood)
- Paresis
(drug therapy, etiology, physiopathology)
- Perceptual Disorders
(drug therapy, etiology, physiopathology)
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