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Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age

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  • William A. Mills

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine
    Medicine, & Health, Virginia Polytechnic Institute and State University)

  • AnnaLin M. Woo

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Shan Jiang

    (Stanford University
    Stanford University)

  • Joelle Martin

    (Medicine, & Health, Virginia Polytechnic Institute and State University)

  • Dayana Surendran

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Matthew Bergstresser

    (Virginia Polytechnic Institute and State University)

  • Ian F. Kimbrough

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Ukpong B. Eyo

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Michael V. Sofroniew

    (University of California)

  • Harald Sontheimer

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

Abstract

Astrocytes extend endfeet that enwrap the vasculature, and disruptions to this association which may occur in disease coincide with breaches in blood-brain barrier (BBB) integrity. Here we investigate if focal ablation of astrocytes is sufficient to disrupt the BBB in mice. Targeted two-photon chemical apoptotic ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes to cover vascular vacancies. In young animals, replacement processes occur in advance of endfoot retraction, but this is delayed in aged animals. Stimulation of replacement astrocytes results in constriction of pre-capillary arterioles, suggesting that replacement astrocytes are functional. Pharmacological inhibition of pSTAT3, as well as astrocyte specific deletion of pSTAT3, reduces astrocyte replacement post-ablation, without perturbations to BBB integrity. Similar endfoot replacement occurs following astrocyte cell death due to reperfusion in a stroke model. Together, these studies uncover the ability of astrocytes to maintain cerebrovascular coverage via substitution from nearby cells.

Suggested Citation

  • William A. Mills & AnnaLin M. Woo & Shan Jiang & Joelle Martin & Dayana Surendran & Matthew Bergstresser & Ian F. Kimbrough & Ukpong B. Eyo & Michael V. Sofroniew & Harald Sontheimer, 2022. "Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29475-2
    DOI: 10.1038/s41467-022-29475-2
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    References listed on IDEAS

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