Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia.
Ann Neurol
; 54(3): 330-42, 2003 Sep.
Article
in En
| MEDLINE
| ID: mdl-12953265
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 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.
Search on Google
Database:
MEDLINE
Therapeutic Methods and Therapies TCIM:
Terapias_biologicas
/
Aromoterapia
Main subject:
Brain
/
Neuroprotective Agents
/
Infarction, Middle Cerebral Artery
/
Nitrogen Oxides
Type of study:
Prognostic_studies
Language:
En
Journal:
Ann Neurol
Year:
2003
Type:
Article
Affiliation country:
United States