Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia

Myron Ginsberg, David A. Becker, Raul Busto, Andrey Belayev, Yongbo Zhang, Larissa Khoutorova, James J. Ley, Weizhao Zhao, Ludmila Belayev

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 ∼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.

Original languageEnglish
Pages (from-to)330-342
Number of pages13
JournalAnnals of Neurology
Volume54
Issue number3
DOIs
StatePublished - Sep 1 2003

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Ischemia
Antioxidants
Stroke
Corpus Striatum
nitrones
stilbazulenyl nitrone
Middle Cerebral Artery Infarction
Neuroprotective Agents
Dimethyl Sulfoxide
Infarction
Sutures
Perfusion
Regression Analysis
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ginsberg, M., Becker, D. A., Busto, R., Belayev, A., Zhang, Y., Khoutorova, L., ... Belayev, L. (2003). Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia. Annals of Neurology, 54(3), 330-342. https://doi.org/10.1002/ana.10659

Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia. / Ginsberg, Myron; Becker, David A.; Busto, Raul; Belayev, Andrey; Zhang, Yongbo; Khoutorova, Larissa; Ley, James J.; Zhao, Weizhao; Belayev, Ludmila.

In: Annals of Neurology, Vol. 54, No. 3, 01.09.2003, p. 330-342.

Research output: Contribution to journalArticle

Ginsberg, M, Becker, DA, Busto, R, Belayev, A, Zhang, Y, Khoutorova, L, Ley, JJ, Zhao, W & Belayev, L 2003, 'Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia', Annals of Neurology, vol. 54, no. 3, pp. 330-342. https://doi.org/10.1002/ana.10659
Ginsberg, Myron ; Becker, David A. ; Busto, Raul ; Belayev, Andrey ; Zhang, Yongbo ; Khoutorova, Larissa ; Ley, James J. ; Zhao, Weizhao ; Belayev, Ludmila. / Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia. In: Annals of Neurology. 2003 ; Vol. 54, No. 3. pp. 330-342.
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