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

• DOI: 10.1016/j.brainres.2004.05.038
• Publication Date: 2004-07-06T15:17:14Z
• Authors: Shaida A Andrabi; Mariarosa G Spina; Peter Lorenz; Uwe Ebmeyer; Gerald Wolf; Thomas F.W Horn
• Keywords: Cerebral Cortex; Male; Neurologic Examination; Neurons; 0301 basic medicine; Analysis of Variance; Cell Death; Dose-Response Relationship, Drug; Cytochromes c; Infarction, Middle Cerebral Artery; Cerebral Infarction; DNA Fragmentation; Epoprostenol; Immunohistochemistry; Brain Ischemia; Mitochondria; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Neuroprotective Agents; Ischemic Attack, Transient; Animals; Microtubule-Associated Proteins

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.