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Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy
Age-related blood-brain barrier disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8680575/ http://dx.doi.org/10.1093/geroni/igab046.2503 |
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author | Toth, Adam Nyul Tarantini, Stefano DelFavero, Jordan Yan, Feng Balasubramanian, Priya Tang, Qinggong Csiszar, Anna Ungvari, Zoltan |
author_facet | Toth, Adam Nyul Tarantini, Stefano DelFavero, Jordan Yan, Feng Balasubramanian, Priya Tang, Qinggong Csiszar, Anna Ungvari, Zoltan |
author_sort | Toth, Adam Nyul |
collection | PubMed |
description | Age-related blood-brain barrier disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to reverse age-related alterations of the cerebral microcirculation for prevention of VCID and AD. To facilitate this research there is an urgent need for sensitive and easy-to-adapt imaging methods, which enable longitudinal assessment of changes in BBB permeability and brain capillarization in aged mice, that could be used in vivo to evaluate treatment efficiency. To enable longitudinal assessment of changes in BBB permeability in aged mice equipped with a chronic cranial window, we adapted and optimized two different intravital two-photon imaging approaches. By assessing relative fluorescence changes over the baseline within a volume of brain tissue, after qualitative image subtraction of the brain microvasculature, we confirmed that in 24 month old C57BL/6J mice cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3 kDa to 40 kDa) is significantly increased as compared to that of 5 month old mice. Real-time recording of vessel cross-sections showed that apparent solute permeability of single microvessels is significantly increased in aged mice vs. young mice. Cortical capillary density, assessed both by intravital two-photon microscopy and optical coherence tomography (OCT) was also decreased in aged mice vs. young mice. The presented methods have been optimized for longitudinal (over the period of 36 weeks) in vivo assessment of cerebromicrovascular health in preclinical geroscience research. |
format | Online Article Text |
id | pubmed-8680575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86805752021-12-17 Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy Toth, Adam Nyul Tarantini, Stefano DelFavero, Jordan Yan, Feng Balasubramanian, Priya Tang, Qinggong Csiszar, Anna Ungvari, Zoltan Innov Aging Abstracts Age-related blood-brain barrier disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to reverse age-related alterations of the cerebral microcirculation for prevention of VCID and AD. To facilitate this research there is an urgent need for sensitive and easy-to-adapt imaging methods, which enable longitudinal assessment of changes in BBB permeability and brain capillarization in aged mice, that could be used in vivo to evaluate treatment efficiency. To enable longitudinal assessment of changes in BBB permeability in aged mice equipped with a chronic cranial window, we adapted and optimized two different intravital two-photon imaging approaches. By assessing relative fluorescence changes over the baseline within a volume of brain tissue, after qualitative image subtraction of the brain microvasculature, we confirmed that in 24 month old C57BL/6J mice cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3 kDa to 40 kDa) is significantly increased as compared to that of 5 month old mice. Real-time recording of vessel cross-sections showed that apparent solute permeability of single microvessels is significantly increased in aged mice vs. young mice. Cortical capillary density, assessed both by intravital two-photon microscopy and optical coherence tomography (OCT) was also decreased in aged mice vs. young mice. The presented methods have been optimized for longitudinal (over the period of 36 weeks) in vivo assessment of cerebromicrovascular health in preclinical geroscience research. Oxford University Press 2021-12-17 /pmc/articles/PMC8680575/ http://dx.doi.org/10.1093/geroni/igab046.2503 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstracts Toth, Adam Nyul Tarantini, Stefano DelFavero, Jordan Yan, Feng Balasubramanian, Priya Tang, Qinggong Csiszar, Anna Ungvari, Zoltan Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy |
title | Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy |
title_full | Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy |
title_fullStr | Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy |
title_full_unstemmed | Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy |
title_short | Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy |
title_sort | demonstration of age-related increase in blood-brain barrier permeability by longitudinal intravital microscopy |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8680575/ http://dx.doi.org/10.1093/geroni/igab046.2503 |
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