Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells.

Abstract:

:Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumours that use the perivascular space for invasion and co-opt existing vessels as satellite tumour form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of preexisting vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over the regulation of vascular tone through Ca(2+)-dependent release of K(+). These findings have important clinical implications regarding blood flow in the tumour-associated brain and the ability to locally deliver chemotherapeutic drugs in disease.

journal_name

Nat Commun

journal_title

Nature communications

authors

Watkins S,Robel S,Kimbrough IF,Robert SM,Ellis-Davies G,Sontheimer H

doi

10.1038/ncomms5196

subject

Has Abstract

pub_date

2014-06-19 00:00:00

pages

4196

issn

2041-1723

pii

ncomms5196

journal_volume

5

pub_type

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