Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia.
In: Annals of neurology, Jg. 54 (2003-09-01), Heft 3, S. 330-42
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Zugriff:
Azulenyl nitrones are novel chain-breaking antioxidants with low oxidation potentials and high lipophilicity-properties favoring their efficacy as neuroprotectants. We tested the second-generation azulenyl nitrone, stilbazunenlyl nitrone (STAZN), in focal ischemic stroke. Physiologically monitored rats received 2 hours of middle cerebral artery occlusion by intraluminal suture, resulting in substantial cortical and striatal infarcation. Neurobehavior was quantified on a standard battery, and brains were perfusion-fixed for quantitative histopathology at 3 days. In 3 independent series, rats were treated at either 2h + 4h, or 2h + 4h + 24h + 48h, after onset of ischemia; vehicle-treated rats received dimethylsulfoxide or saline. All animals (n = 52) developed high-grade neurological deficits (score 11 of 12) during ischemia, which improved, in STAZN-treated rats, within 1-1.5 h of the initial dose and fell to a median score of 3 at 72 h, compared to 8 in vehicle rats. STAZN treatment reduced mean cortical infarct volume by 64-97%, and total infarct volume by 42-72%. In over one-half of STAZN-treated animals, cortical infarction was virtually abolished. Regression analysis predicted that STAZN would confer approximately 50% cortical neuroprotection even in the most severely affected cases. The potency of STAZN was orders-of-magnitude greater than other nitrones such as NXY-059. These results suggest that STAZN has great promise for ischemic stroke.
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Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia.
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Autor/in / Beteiligte Person: | Ginsberg, MD ; Becker, DA ; Busto, R ; Belayev, A ; Zhang, Y ; Khoutorova, L ; Ley, JJ ; Zhao, W ; Belayev, L |
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Zeitschrift: | Annals of neurology, Jg. 54 (2003-09-01), Heft 3, S. 330-42 |
Veröffentlichung: | New York, NY : Wiley-Liss ; <i>Original Publication</i>: Boston, Little, Brown., 2003 |
Medientyp: | academicJournal |
ISSN: | 0364-5134 (print) |
DOI: | 10.1002/ana.10659 |
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