Oxyresveratrol ( trans-2,3′,4,5′-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia

• Published in: Brain research 2004-08, Vol.1017 (1), p.98-107
• Main Authors: Andrabi, Shaida A, Spina, Mariarosa G, Lorenz, Peter, Ebmeyer, Uwe, Wolf, Gerald, Horn, Thomas F.W
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Apoptosis; Biological and medical sciences; Brain infarct; Brain Ischemia - prevention & control; Cell Death - drug effects; Cerebral Cortex - drug effects; Cerebral Cortex - pathology; Cerebral Infarction - drug therapy; Cerebral Infarction - pathology; Cytochromes c - metabolism; Disease Models, Animal; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; Epoprostenol - analogs & derivatives; Hydroxystilbene; Immunohistochemistry - methods; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Ischemia; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - metabolism; Male; MCAO; Medical sciences; Microtubule-Associated Proteins - metabolism; Middle cerebral artery occlusion; Mitochondria - drug effects; Natural compound; Neurologic Examination - methods; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotection; Neuroprotective agent; Neuroprotective Agents - therapeutic use; Pharmacology. Drug treatments; Phosphopyruvate Hydratase - metabolism; Plant Extracts - therapeutic use; Rats; Rats, Wistar; Stilbenes - therapeutic use; Stroke; Time Factors
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.05.038

Oxidative stress is one of the major pathological factors in the cascade that leads to cell death in cerebral ischemia. Here, we investigated the neuroprotective effect of a naturally occurring antioxidant, oxyresveratrol, to reduce brain injury after cerebral stroke. We used the transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia to induce a defined brain infarction. Oxyresveratrol was given twice intraperitoneally: immediately after occlusion and at the time of reperfusion. Oxyresveratrol (10 or 20 mg/kg) significantly reduced the brain infarct volume by approximately 54% and 63%, respectively, when compared to vehicle-treated MCAO rats. Also, the neurological deficits as assessed by different scoring methods improved in oxyresveratrol-treated MCAO rats. Histological analysis of apoptotic markers in the ischemic brain area revealed that oxyresveratrol treatment diminished cytochrome c release and decreased caspase-3 activation in MCAO rats. Also, staining for apoptotic DNA showed that the number of apoptotic nuclei in ischemic brain was reduced after oxyresveratrol treatment as compared to the vehicle-treated MCAO rats. This dose-dependent neuroprotective effect of oxyresveratrol in an in vivo stroke model demonstrates that this drug may prove to be beneficial for a therapeutic strategy to limit brain injury in acute brain ischemia.