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

Stacey Watkins | Stefanie Robel | Ian F Kimbrough | Stephanie M Robert | Graham Ellis-Davies | Harald Sontheimer
Nature communications | 2014

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.

Pubmed ID: 24943270

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: 1F31NS074597
  • Agency: NINDS NIH HHS, United States
    Id: P30 NS057098
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS031234
  • Agency: NINDS NIH HHS, United States
    Id: NS57098
  • Agency: NINDS NIH HHS, United States
    Id: T32 NS048039
  • Agency: NINDS NIH HHS, United States
    Id: 2R01NS036692
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS036692
  • Agency: NINDS NIH HHS, United States
    Id: NS047466
  • Agency: NINDS NIH HHS, United States
    Id: P30 NS047466
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS082851
  • Agency: NINDS NIH HHS, United States
    Id: 1R01NS082851
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS074597
  • Agency: NICHD NIH HHS, United States
    Id: P30 HD038985
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS069720
  • Agency: NINDS NIH HHS, United States
    Id: 5R01NS031234
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM053395

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