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

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 viv...

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Published in:Nature communications 2022-10, Vol.13 (1), p.5912-19, Article 5912
Main Authors: Berthiaume, Andrée-Anne, Schmid, Franca, Stamenkovic, Stefan, Coelho-Santos, Vanessa, Nielson, Cara D., Weber, Bruno, Majesky, Mark W., Shih, Andy Y.
Format: Article
Language:English
Subjects:
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Ablation
Aging
Animals
Blood flow
Blood vessels
Blood-brain barrier
Brain - blood supply
Brain architecture
Capillaries
Capillary flow
Cerebral blood flow
Dementia disorders
Dilation
Disruption
Heterogeneity
Humanities and Social Sciences
In vivo methods and tests
Mice
multidisciplinary
Neural networks
Neuroimaging
Pericytes
Science
Science (multidisciplinary)
Therapeutic targets
Veins
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Summary: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. Using in vivo two-photon imaging, Berthiaume et al. demonstrate how pericyte loss during aging could contribute to deterioration of cerebral blood flow. They also show how pericyte remodeling reduces the deleterious effects of pericyte loss.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33464-w