Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 10 2022
07 10 2022
Historique:
received:
27
08
2021
accepted:
14
09
2022
entrez:
7
10
2022
pubmed:
8
10
2022
medline:
12
10
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36207315
doi: 10.1038/s41467-022-33464-w
pii: 10.1038/s41467-022-33464-w
pmc: PMC9547063
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5912Subventions
Organisme : NIA NIH HHS
ID : R01 AG062738
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS097775
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG063031
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS106138
Pays : United States
Informations de copyright
© 2022. The Author(s).
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