Elsevier

Neuroscience

Volume 115, Issue 1, 15 November 2002, Pages 145-152
Neuroscience

Expression of caveolin-1 in human brain microvessels

https://doi.org/10.1016/S0306-4522(02)00374-3Get rights and content

Abstract

Caveolae are microinvaginations of the cell plasma membrane involved in cell transport and metabolism as well as in signal transduction; these functions depend on the presence of integral proteins named caveolins in the caveolar frame. In the brain, various caveolin subtypes have been detected in vivo by immunocytochemistry: caveolin-1 and -2 were found in rat brain microvessels, caveolin-3 was revealed in astrocytes. The aim of this study was to identify the site(s) of cellular expression of caveolin-1 in the microvessels of the human cerebral cortex by immunofluorescence confocal microscopy and immunogold electron microscopy. Since in the barrier-provided brain microvessels tight relations occur between the endothelium–pericyte layer and the surrounding vascular astrocytes, double immunostaining with caveolin-1 and the astroglia marker, glial fibrillary acidic protein, was also carried out. Immunocytochemistry by confocal microscopy revealed that caveolin-1 is expressed by endothelial cells and pericytes in all the cortex microvessels; caveolin-1 is also expressed by cells located in the neuropil around the microvessels and identified as astrocytes. Study of the cortex microvessels carried out by immunoelectron microscopy confirmed that in the vascular wall caveolin-1 is expressed by endothelial cells, pericytes, and vascular astrocytes, and revealed the association of caveolin-1 with the cell caveolar compartment. The demonstration of caveolin-1 in the cells of the brain microvessels suggests that caveolin-1 may be involved in blood–brain barrier functioning, and also supports co-ordinated activities between these cells.

Section snippets

Experimental procedures

Small pieces of adult human cerebral cortex of the parietal lobe, obtained at 10 diagnostic biopsies (patient age 50–60 years), were sampled and submitted to conventional histopathological analysis. Samples evaluated as histologically normal were utilised in this study.

Caveolin-1 and GFAP immunofluorescence confocal microscopy

In the human cerebral cortex, caveolin-1 immunoreactivity is detected on all the cortex microvessels and also on bodies of astrocyte-like cells that extend fine processes ending on the microvessel wall (Fig. 1A). At a distance from the microvessels, caveolin-1 immunoreactivity is only detectable as fluorescent puncta scattered in the neuropil (Fig. 1A). On the projection images, the staining pattern of caveolin-1 is finely punctate and evenly distributed on the wall of the microvessels, being

Discussion

Brain microvessels are the site of the BBB, a selective gate that controls the exchange of solutes, ions, nutrients, drugs, as well as immunological cells, between the blood and the brain. In the cerebral microvessel, besides the lining formed by ‘impermeable’ endothelial cells, poor in transport vesicles and sealed by tight junctions, and functionally characterised by specific enzymatic and transport systems (Reese and Karnovsky, 1967, Vorbrodt, 1988, Dermietzel and Krause, 1991), two other

Acknowledgements

We thank Giancarlo Amendoni, MD, for the linguistic help. This work was supported by grants from ‘Consiglio Nazionale delle Ricerche’ (CNR, to L.R.) and ‘Ministero dell’Istruzione, dell’Università e della Ricerca’ (MIUR, to D.V.).

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