Defective associations between blood vessels and brain parenchyma lead to cerebral hemorrhage in mice lacking alphav integrins.
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.
McCarty
Joseph H
JH
Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Monahan-Earley
Rita A
RA
Brown
Lawrence F
LF
Keller
Markus
M
Gerhardt
Holger
H
Rubin
Kristofer
K
Shani
Moshe
M
Dvorak
Harold F
HF
Wolburg
Hartwig
H
Bader
Bernhard L
BL
Dvorak
Ann M
AM
Hynes
Richard O
RO
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
D039564:Integrin alphaV; D039641:Integrin beta Chains; C094865:integrin beta8; D012260:Ribonucleases