E15.5 Tfpi^−/−embryos lacking FV had normal cerebral vasculature. (A) Trichrome-stained midbrain from a F5^+/−Tfpi^−/− embryo had a large area of hemorrhage (asterisk) and necrosis surrounded by glomeruloid bodies, essentially identical to that observed in Tfpi^−/− embryos. In contrast, F5^−/−Tfpi^−/− embryos had normal brain vasculature without evidence of glomeruloid bodies, hemorrhage, or cellular death. Glomeruloid bodies were seen surrounded by fibrinogen (brackets) leaking from the abnormal vessels. The dotted line delineated the brain tissue with massive cell death (right) from that of the living cells (left). Normal architecture of the F5^−/−Tfpi^−/− embryo brain displayed normal vasculature without fibrinogen leakage. Laminin staining of the F5^+/−Tfpi^−/− brain revealed numerous glomeruloid bodies throughout the brain parenchyma (arrows point to 3 glomeruloid bodies). The dotted line delineates cell death (right) from living cells (left). The F5^−/−Tfpi^−/− brain had normal vasculature with laminin-stained basement membrane. Scale bars, 100 µm. (B) Trichrome stain of pial vessels (arrows) penetrating the brain parenchyma in the F5^+/−Tfpi^−/− embryo (left) and F5^−/−Tfpi^−/− embryo (right). The penetrating vasculature of the F5^+/−Tfpi^−/− embryo revealed glomeruloid bodies advancing from the disorganized pia mater, while the vasculature from the F5^−/−Tfpi^−/− embryo is organized with parallel walls (scale bar, 50 µm). (C) Trichrome-stained sections from F5^−/−Tfpi^−/− embryos carrying the F5^LiverTg. Rare glomeruloid bodies were observed in the midbrain of one embryo (arrows) and spinal cord of another embryo (sc; square). Minor hemorrhage is present in the spinal cord but is not associated with cell death or inflammation. No pathology was observed in 3 other F5^−/−F5^LiverTgTfpi^−/− embryos (scale bar, 100 µm).