title: Defective associations between blood vessels and brain parenchyma lead to cerebral hemorrhage in mice lacking alphav integrins.
abstract: Mouse embryos genetically null for the alphav integrin subunit develop intracerebral hemorrhages at midgestation and die shortly after birth. A key question is whether the hemorrhage arises from primary defects in vascular endothelial cells or pericytes or from other causes. We have previously reported normal initiation of cerebral vessels comprising branched tubes of endothelial cells. Here we show that the onset of hemorrhage is not due to defects in pericyte recruitment. Additionally, most alphav-null vessels display ultrastructurally normal endothelium-pericyte associations and normal interendothelial cell junctions. Thus, endothelial cells and pericytes appear to establish their normal relationships in cerebral microvessels. However, by both light and electron microscopy, we detected defective associations between cerebral microvessels and the surrounding brain parenchyma, composed of neuroepithelial cells, glia, and neuronal precursors. These data suggest a novel role for alphav integrins in the association between cerebral microvessels and central nervous system parenchymal cells.
authors.affiliation: Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: McCarty
authors.forename: Rita A
authors.initials: RA
authors.lastname: Monahan-Earley
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Brown
authors.forename: Markus
authors.initials: M
authors.lastname: Keller
authors.forename: Holger
authors.initials: H
authors.lastname: Gerhardt
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
authors.forename: Moshe
authors.initials: M
authors.lastname: Shani
authors.forename: Harold F
authors.initials: HF
authors.lastname: Dvorak
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Bernhard L
authors.initials: BL
authors.lastname: Bader
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dvorak
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D002455:Cell Division; D002490:Central Nervous System / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006579:Heterozygote; D007150:Immunohistochemistry; D039564:Integrin alphaV / Q000235:genetics* / Q000502:physiology*; D039641:Integrin beta Chains / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic; D009457:Neuroglia / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012260:Ribonucleases / Q000378:metabolism; D013687:Telencephalon / Q000098:blood supply / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D039564:Integrin alphaV; D039641:Integrin beta Chains; C094865:integrin beta8; D012260:Ribonucleases