2,536 research outputs found
Immunocytochemical detection of caveolin-1 by confocal microscopy in human brain. It. J. Anat. Embryol. :,
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Immunohistochemical and ultrastructural characterization of cortical plate microvasculature in the human fetus telencephalon
No full textThe blood-brain barrier (BBB) differentiation was investigated by immunohistochemistry and electron microscopy in the radial microvasculature of the telencephalon cortical plate (CP) of 12- and 18-week human fetuses. The BBB-specific glucose transporter isoform 1 (GLUT1) is expressed in both stages, with a main localization on the ablumenal and lateral plasma membranes of the endothelial cells. The endothelial cells are welded by short junctions with fusion points of the plasma membranes at 12 weeks and by extensive tight junctions at 18 weeks. The basal lamina is discontinuous beneath the endothelium-pericyte layer at 12 weeks and splits into two continuous layers circumscribing the pericytes in the later stage. The expression of laminin, a basal lamina glycoprotein, is continuous already at 12 weeks. The CP microvessels are tightly surrounded by processes of glial cells. Immunodetection of the cytoskeletal filament proteins, vimentin (VIM), and glial fibrillary acidic protein (GFAP), demonstrates that at 12 weeks the perivascular glial processes are mostly represented by VIM-stained fibers of the radial glia. At 18 weeks, GFAP-stained radial glia fibers, processes of VIM-stained astroblasts, and GFAP-positive astrocytes also build the perivascular envelopes. The results indicate that the vessel differentiation is already under way in the human CP at the midgestational age and entails the establishment of some barrier devices. The early relationship between perivascular glia coverage formation and endothelial barrier maturation suggests that also immature astroglial cells are involved in the setting up of the BBB
Expression of P-glycoprotein in human cerebral cortex microvessels
No full textP-Glycoprotein (P-gp) is an ATP-dependent efflux transporter that extrudes non-polar molecules, including cytotoxic substances and drugs, from the cells. It was initially found in cancer cells and then was shown to be a normal component of complex transport systems working at the blood-brain barrier (BBB). Previous studies have demonstrated that, in the brain, P-gp is localized on the luminal plasmalemma of BBB endothelial cells and that it may interact with the caveolar compartment of these cells. The aim of this study was to identify the site of cellular expression of P-gp in human brain in situ and to morphologically determine whether an association may exist between P-gp and caveolin-1, a structural and functional protein of the caveolar frame. The study was carried out on human cerebral cortex by immunoconfocal microscopy with antibodies to both P-gp and caveolin-1. The results show that P-gp marks the microvessels of the cortex and that the transporter is localized in the luminal endothelial compartment, where it co-localizes with caveolin-1. The demonstration of this co-localization of P-gp with caveolin-1 contributes a morphological backing to biochemical studies on P-gp/caveolin-1 relationships and leads us to suggest that interactions between these molecules may occur at the BBB endothelia
An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis
No full textIn order to better understand the process of angiogenesis in the developing human brain, we have examined the spatial relationship and relative contributions of endothelial cells and pericytes, the two primary cell types involved in vessel growth, together with their relation with the vascular basement membrane. Pericytes were immunolocalized through use of the specific markers nerve/glial antigen 2 (NG2) proteoglycan, endosialin (CD248) and the platelet-derived growth factor receptor beta (PDGFR-beta), while endothelial cells were identified by the pan-endothelial marker CD31 and the blood brain barrier (BBB)-specific markers claudin-5 and glucose transporter isoform 1 (GLUT-1). The quantitative analysis demonstrates that microvessels of the fetal human telencephalon are characterized by a continuous layer of activated/angiogenic NG2 pericytes, which tightly invest endothelial cells and participate in the earliest stages of vessel growth. Immunolabelling with anti-active matrix metalloproteinase-2 (aMMP-2) and anti-collagen type IV antibodies revealed that aMMP-2 producing endothelial cells and pericytes are both associated with the vascular basement membrane during vessel sprouting. Detailed localization of the two vascular cell types during angiogenesis suggests that growing microvessels of the human telencephalon are formed by a pericyte-driven angiogenic process in which the endothelial cells are preceded and guided by migrating pericytes during organization of the growing vessel wall
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