Novel situations of endothelial injury in stroke--mechanisms of stroke and strategy of drug development: protective effects of antiplatelet agents against stroke.

Stroke is the second cause of mortality worldwide, and intravenous administration of tissue plasminogen activator (t-PA) within 3 h of symptom onset is the only treatment proven effective for re-establishment of cerebral blood flow following acute ischemic stroke. However, its widespread application remains limited by its narrow therapeutic time window and the related risks of intracranial hemorrhage. On the other hand, in patients with atherothrombotic risk, antiplatelet agents are widely used to decrease the risk of occlusive arterial events. All of these drugs are used during coronary interventions and in the medical management of acute coronary syndromes. In contrast, only aspirin, cilostazol, and thienopyridine derivatives (ticlopidine and clopidogrel) are used in the long-term prevention of cerebrovascular events in patients with risk of recurrence. In this paper, we introduce recent clinical findings on antiplatelet therapies for secondary prevention after ischemic stroke and describe basic research that has focused on cerebrovascular protection by cilostazol, which has a unique pharmacological profile.