Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age
William A. Mills,
AnnaLin M. Woo,
Shan Jiang,
Joelle Martin,
Dayana Surendran,
Matthew Bergstresser,
Ian F. Kimbrough,
Ukpong B. Eyo,
Michael V. Sofroniew and
Harald Sontheimer (nkn7mv@virginia.edu)
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William A. Mills: University of Virginia School of Medicine
AnnaLin M. Woo: University of Virginia School of Medicine
Shan Jiang: Stanford University
Joelle Martin: Medicine, & Health, Virginia Polytechnic Institute and State University
Dayana Surendran: University of Virginia School of Medicine
Matthew Bergstresser: Virginia Polytechnic Institute and State University
Ian F. Kimbrough: University of Virginia School of Medicine
Ukpong B. Eyo: University of Virginia School of Medicine
Michael V. Sofroniew: University of California
Harald Sontheimer: University of Virginia School of Medicine
Nature Communications, 2022, vol. 13, issue 1, 1-15
Abstract:
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.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29475-2
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DOI: 10.1038/s41467-022-29475-2
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