Platelet-derived VWF alone mediates ischemic stroke injury. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the right middle cerebral artery, followed by 23 hours of reperfusion in WT (n = 12), VWF KO (n = 10), VWF PLT chimeric (n = 16), and VWF EC chimeric (n = 9) mice. (A) Representative 2,3,5-triphenyltetrazolium chloride staining of 3 consecutive coronal brain sections 24 hours after induction of transient middle cerebral artery occlusion (tMCAO) are shown. White color indicates infarcted area, whereas a pink color shows unaffected brain tissue. (B) Brain infarct volumes as quantified by planimetric analysis 24 hours after tMCAO. (C) To exclude potential irradiation-mediated effects on cerebral injury, transient focal cerebral ischemia was induced in irradiated VWF KO mice transplanted with MNCs derived from VWF KO mice (VWF KO + VWF KO PLTs). Planimetric analysis of brain infarct volumes 24 hours after tMCAO in WT (n = 5), VWF KO (n = 7), and VWF KO + VWF KO PLTs chimeric mice (n = 7). ns, not statistically significant. *P < .05; **P < .01.