title: Oxyresveratrol (trans-2,3',4,5'-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia.
abstract: 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.
authors.affiliation: Institute for Medical Neurobiology, Otto-von-Guericke University Magdeburg, Leipziger Strasse-44, Haus 36, D-39120, Magdeburg, Germany.
authors.forename: Shaida A
authors.initials: SA
authors.lastname: Andrabi
authors.forename: Mariarosa G
authors.initials: MG
authors.lastname: Spina
authors.forename: Peter
authors.initials: P
authors.lastname: Lorenz
authors.forename: Uwe
authors.initials: U
authors.lastname: Ebmeyer
authors.forename: Gerald
authors.initials: G
authors.lastname: Wolf
authors.forename: Thomas F W
authors.initials: TF
authors.lastname: Horn
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000031:analogs & derivatives*; D007150:Immunohistochemistry / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D009460:Neurologic Examination / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013267:Stilbenes / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D013267:Stilbenes; C068518:TTC 909; C034912:puag-haad; D045304:Cytochromes c; D011464:Epoprostenol; D010751:Phosphopyruvate Hydratase