Effects of aging and HIF-1alpha deficiency on permeability of hippocampal vessels.
We examined age-related changes in the blood-brain barrier (BBB) of neural cell-specific hypoxia inducible factor-1alpha (HIF-1alpha) deficient mice, which showed hydrocephalus with neuronal cell loss, to investigate an effect of neural cell-specific HIF-1alpha deficiency or hydrocephalus on vascular function. Vascular permeability of horseradish peroxidase (HRP) and binding of cationized ferritin (CF) particles to the endothelial cell luminal surface, as a marker of glycocalyx, were investigated. The thickness of CF-labeled glycocalyx was significantly decreased in the cortex in mutant mice compared with that of control mice, although it was not paralleled by increased vascular permeability. In addition, strong staining for HRP was seen around vessels located along the hippocampal fissure in 24-month-old mutant mice. The reaction product of HRP appeared in an increasing number of the endothelial cell abluminal vesicles and within the thickened basal lamina of arterioles in the hippocampus, showing increased vascular permeability. There were no leaky vessels in 10-week-old mutant mice or 10-week-old and 24-month-old control mice. These findings suggest the necessity of two factors, aging and hydrocephalus, for BBB dysfunction in HIF-1alpha deficient mice.
Ueno
Masaki
M
Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. masaueno@med.kagawa-u.ac.jp
Tomita
Shuhei
S
Nakagawa
Toshitaka
T
Ueki
Masaaki
M
Iwanaga
Yasuyuki
Y
Ono
Jun-Ichiro
J
Onodera
Masayuki
M
Huang
Cheng-Long
CL
Kanenishi
Kenji
K
Shimada
Atsuyoshi
A
Maekawa
Nobuhiro
N
Sakamoto
Haruhiko
H
D000375:Aging; D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D001808:Blood Vessels / Q000502:physiology / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000502:physiology*; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000166:cytology; D005293:Ferritins / Q000378:metabolism; D019276:Glycocalyx; D006624:Hippocampus / Q000098:blood supply*; D006735:Horseradish Peroxidase; D006849:Hydrocephalus / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency*; D051379:Mice; D008853:Microscopy; D046529:Microscopy, Electron, Transmission; D022161:Transport Vesicles / Q000648:ultrastructure
C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005293:Ferritins; D006735:Horseradish Peroxidase