Lack of antiapoptotic effects of antiplatelet drug, aspirin and clopidogrel, and antioxidant, MCI-186, against focal ischemic brain damage in rats

Objectives: This study evaluated the antiapoptotic effect of antiplatelet drugs, aspirin and clopidogrel, and the antioxidant drug, MCI-186, against focal cerebral ischemic rat brain damage. Methods: Cerebral ischemia was mechanically induced by 2-hour occlusion of the left middle cerebral artery (MCA) using an intraluminal filament followed by 24-hour reperfusion. Results: The cerebral infarct size was little affected by oral administration of 300 mg/kg aspirin, 30 mg/kg clopidogrel or 100 mg/kg MCl-186, but was significantly reduced by 30 mg/kg cilostazol. However, intravenous a ministration of 10 mg/kg MCl-186 suppressed the intarct size. DNA fragmentation observed in the cortical tissues corresponding to the penumbral zone was not suppressed by aspirin, clopidogrel or MCl-186, but was significantly suppressed by cilostazol. Increased phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and Bax protein, and decreased Akt/cyclic AMP response element binding protein (CREB) phosphory/ation, including Bcl-2 protein in the vehicle-treated group were not affected by treatment with aspirin, clopidogrel and MCI-186, whereas those effects were reversed by cilostazol. Conclusion: Thus, it is suggested that antiplatelet drugs, aspirin and clopidogrel, and antioxidant drug, MCl-186, showed little antiapoptotic effect in contrast to cilostazol.