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Brain capillary pericytes exert a substantial but slow influence on blood flow

The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their...

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Autores principales: Hartmann, David A., Berthiaume, Andrée-Anne, Grant, Roger I., Harrill, Sarah A., Koski, Tegan, Tieu, Taryn, McDowell, Konnor P., Faino, Anna V., Kelly, Abigail L., Shih, Andy Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102366/
https://www.ncbi.nlm.nih.gov/pubmed/33603231
http://dx.doi.org/10.1038/s41593-020-00793-2
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author Hartmann, David A.
Berthiaume, Andrée-Anne
Grant, Roger I.
Harrill, Sarah A.
Koski, Tegan
Tieu, Taryn
McDowell, Konnor P.
Faino, Anna V.
Kelly, Abigail L.
Shih, Andy Y.
author_facet Hartmann, David A.
Berthiaume, Andrée-Anne
Grant, Roger I.
Harrill, Sarah A.
Koski, Tegan
Tieu, Taryn
McDowell, Konnor P.
Faino, Anna V.
Kelly, Abigail L.
Shih, Andy Y.
author_sort Hartmann, David A.
collection PubMed
description The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and pre-capillary arterioles. This slow vasoconstriction was inhibited by the clinically-used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically-induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.
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spelling pubmed-81023662021-08-18 Brain capillary pericytes exert a substantial but slow influence on blood flow Hartmann, David A. Berthiaume, Andrée-Anne Grant, Roger I. Harrill, Sarah A. Koski, Tegan Tieu, Taryn McDowell, Konnor P. Faino, Anna V. Kelly, Abigail L. Shih, Andy Y. Nat Neurosci Article The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and pre-capillary arterioles. This slow vasoconstriction was inhibited by the clinically-used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically-induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain. 2021-02-18 2021-05 /pmc/articles/PMC8102366/ /pubmed/33603231 http://dx.doi.org/10.1038/s41593-020-00793-2 Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Hartmann, David A.
Berthiaume, Andrée-Anne
Grant, Roger I.
Harrill, Sarah A.
Koski, Tegan
Tieu, Taryn
McDowell, Konnor P.
Faino, Anna V.
Kelly, Abigail L.
Shih, Andy Y.
Brain capillary pericytes exert a substantial but slow influence on blood flow
title Brain capillary pericytes exert a substantial but slow influence on blood flow
title_full Brain capillary pericytes exert a substantial but slow influence on blood flow
title_fullStr Brain capillary pericytes exert a substantial but slow influence on blood flow
title_full_unstemmed Brain capillary pericytes exert a substantial but slow influence on blood flow
title_short Brain capillary pericytes exert a substantial but slow influence on blood flow
title_sort brain capillary pericytes exert a substantial but slow influence on blood flow
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102366/
https://www.ncbi.nlm.nih.gov/pubmed/33603231
http://dx.doi.org/10.1038/s41593-020-00793-2
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