[Protective effects of cilostazol against transient focal cerebral ischemia and hemorrhagic transformation].

Cilostazol, a selective inhibitor of phosphodiesterase III, is an antiplatelet drug and a vasodilator via increased cAMP levels. It has been approved for the treatment of ischemic symptoms in chronic peripheral arterial obstruction or intermittent claudication and for secondary prevention of cerebral infarction (CSPS I). Recently, cilostazol has been reported to be more effective than aspirin in the secondary prevention of all types of stroke in patients and, in particular, prevent the secondary attack of hemorrhagic stroke in patients (CSPS II). Laboratory investigations revealed that cilostazol has a neuroprotective effect against ischemic brain injury. The neuroprotective potential is dependent on its antiinflammatory and antiapoptotic effects mediated by scavenging hydroxyl radicals, decreasing formation of tumor necrosis factor-α, and inhibition of poly (ADP-ribose) polymerase activity. In addition, increasing evidence indicates that cilostazol may offer endothelial protection via both the inhibition of lipopolysaccharide-induced apoptosis and induced nitric oxide (NO) production by endothelial NO synthase activation. The breakdown of the barrier permeability of the blood brain barrier (BBB) often accelerates the progression of diseases such as cerebral ischemia. However, the molecular mechanisms involved in BBB disruption have not been fully determined. Identification of the molecules responsible for the disruption of the endothelial barrier may yield new therapeutic targets in intractable diseases. This article reviews the protective effects of cilostazol against transient focal cerebral ischemia and hemorrhagic transformation and its mechanism of action.