Evidence for a role for both platelet aggregation and secretion in maintaining cerebral vascular integrity. (A) Mice deficient in the major platelet integrin subinit αIIb present with cerebral hemorrhaging at E12.5 (black arrows; 6 of 6 αIIb^−/− embryos). Hemorrhages were also observed in 6 of 8 embryos at E12.5 from mice in which both platelet α-granule and dense-granule secretion is abolished (black arrows; Nbeal-2^−/−Unc13d^−/−). Scale bars, 1 mm. (B) H&E coronal sections from E12.5 embryo heads show the accumulation of erythrocytes in the ventricles of αIIb^−/− (n = 6) and Nbeal-2^−/−Unc13d^−/− (n = 6 of 8) embryos (red arrows), whereas only a minor hemorrhage was observed in 1 of 17 wild-type littermate controls (^+/+). White boxes show magnified areas in the lower panel. Scale bars, 50 μm.