BACKGROUND AND PURPOSE: Ticagrelor is a novel P2Y12 antagonist, and little is known about its efficacy and safety in the endovascular treatment of aneurysms. This study evaluated the efficacy and safety of ticagrelor versus clopidogrel for stent-assisted coiling or flow-diversion treatment in patients with unruptured cerebral aneurysms. MATERIALS AND METHODS: From November 2003 to February 2019, two hundred one patients (mean age, 57.5 years; 156 women) with 233 unruptured aneurysms underwent stent-assisted coiling or flow-diversion treatment. All patients received antiplatelet therapy of aspirin plus clopidogrel (clopidogrel group, 121 patients with 140 aneurysms) or aspirin plus ticagrelor (ticagrelor group, 80 patients with 93 aneurysms). The clinical and radiologic data in each group were retrospectively reviewed and compared. RESULTS: Two hundred thirty-six procedures were performed, including stent-assisted coiling (n = 101) and flow diversion (n = 135). At 90 days, the primary outcome—a composite of any stroke and death—occurred in 9.9% of the clopidogrel group and 8.6% of the ticagrelor group (P = .822). Ischemic stroke occurred in 10 (7.0%) of the clopidogrel group and 7 (7.5%) of the ticagrelor group (P > .999). Disabling stroke occurred in 4 (2.8%) in the clopidogrel group and in 4 (4.3%) in the ticagrelor group (P = .716). Ninety-day death occurred in 3 (2.1%) in the clopidogrel group and 1 (1.1%) in the ticagrelor group (P > .999). Any bleeding at 90 days occurred in 13 (9.2%) in the clopidogrel group and 6 (6.5%) in the ticagrelor group (P = .479). CONCLUSIONS: Ticagrelor appears to be as effective and safe as clopidogrel in stent-assisted coiling or flow-diversion treatment for unruptured cerebral aneurysms.

Ischemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not been fully clarified. In this study, we found that the P2X4 receptor, which is abundantly expressed in vascular endothelial cells, is required for ischemic tolerance following middle artery occlusion (MCAO) in mice. Mechanistically, the P2X4 receptor was stimulated by fluid shear stress, which mimics reperfusion, thus promoting the increased expression of osteopontin, a neuroprotective molecule. Furthermore, we found that the intracerebroventricular administration of osteopontin was sufficient to exert a neuroprotective effect mediated by preconditioning-stimulated P2X4 receptor activation. These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance.