Header

UZH-Logo

Maintenance Infos

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


Berthiaume, Andrée-Anne; Schmid, Franca; Stamenkovic, Stefan; Coelho-Santos, Vanessa; Nielson, Cara D; Weber, Bruno; Majesky, Mark W; Shih, Andy Y (2022). Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure. bioRxiv 489881, Cold Spring Harbor Laboratory.

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.

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.

Statistics

Citations

Dimensions.ai Metrics

22 citations in Scopus®

Altmetrics

Downloads

19 downloads since deposited on 01 Nov 2022
11 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Working Paper
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Physical Sciences > General Chemistry
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Health Sciences > Multidisciplinary
Physical Sciences > General Physics and Astronomy
Language:English
Date:21 August 2022
Deposited On:01 Nov 2022 10:40
Last Modified:27 May 2024 15:23
Series Name:bioRxiv
ISSN:2164-7844
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/2022.04.28.489881
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)