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Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure

Author

Listed:
  • Andrée-Anne Berthiaume

    (Seattle Children’s Research Institute
    Medical University of South Carolina)

  • Franca Schmid

    (ETH Zurich
    Institute of Pharmacology and Toxicology, University of Zurich)

  • Stefan Stamenkovic

    (Seattle Children’s Research Institute)

  • Vanessa Coelho-Santos

    (Seattle Children’s Research Institute)

  • Cara D. Nielson

    (Seattle Children’s Research Institute
    Graduate Program in Neuroscience, University of Washington)

  • Bruno Weber

    (Institute of Pharmacology and Toxicology, University of Zurich
    Neuroscience Center Zurich, University and ETH Zurich)

  • Mark W. Majesky

    (Seattle Children’s Research Institute
    University of Washington)

  • Andy Y. Shih

    (Seattle Children’s Research Institute
    Medical University of South Carolina
    University of Washington
    University of Washington)

Abstract

Deterioration of brain capillary flow and architecture is a hallmark of aging and dementia. It remains unclear how loss of brain pericytes in these conditions contributes to capillary dysfunction. Here, we conduct cause-and-effect studies by optically ablating pericytes in adult and aged mice in vivo. Focal pericyte loss induces capillary dilation without blood-brain barrier disruption. These abnormal dilations are exacerbated in the aged brain, and result in increased flow heterogeneity in capillary networks. A subset of affected capillaries experience reduced perfusion due to flow steal. Some capillaries stall in flow and regress, leading to loss of capillary connectivity. Remodeling of neighboring pericytes restores endothelial coverage and vascular tone within days. Pericyte remodeling is slower in the aged brain, resulting in regions of persistent capillary dilation. These findings link pericyte loss to disruption of capillary flow and structure. They also identify pericyte remodeling as a therapeutic target to preserve capillary flow dynamics.

Suggested Citation

  • Andrée-Anne Berthiaume & Franca Schmid & Stefan Stamenkovic & Vanessa Coelho-Santos & Cara D. Nielson & Bruno Weber & Mark W. Majesky & Andy Y. Shih, 2022. "Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33464-w
    DOI: 10.1038/s41467-022-33464-w
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    References listed on IDEAS

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