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Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter...

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Autores principales: Huuskonen, Mikko T., Liu, Qinghai, Lamorie-Foote, Krista, Shkirkova, Kristina, Connor, Michelle, Patel, Arati, Montagne, Axel, Baertsch, Hans, Sioutas, Constantinos, Morgan, Todd E., Finch, Caleb E., Zlokovic, Berislav V., Mack, William J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635097/
https://www.ncbi.nlm.nih.gov/pubmed/34868068
http://dx.doi.org/10.3389/fimmu.2021.785519
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author Huuskonen, Mikko T.
Liu, Qinghai
Lamorie-Foote, Krista
Shkirkova, Kristina
Connor, Michelle
Patel, Arati
Montagne, Axel
Baertsch, Hans
Sioutas, Constantinos
Morgan, Todd E.
Finch, Caleb E.
Zlokovic, Berislav V.
Mack, William J.
author_facet Huuskonen, Mikko T.
Liu, Qinghai
Lamorie-Foote, Krista
Shkirkova, Kristina
Connor, Michelle
Patel, Arati
Montagne, Axel
Baertsch, Hans
Sioutas, Constantinos
Morgan, Todd E.
Finch, Caleb E.
Zlokovic, Berislav V.
Mack, William J.
author_sort Huuskonen, Mikko T.
collection PubMed
description Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations.
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spelling pubmed-86350972021-12-02 Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion Huuskonen, Mikko T. Liu, Qinghai Lamorie-Foote, Krista Shkirkova, Kristina Connor, Michelle Patel, Arati Montagne, Axel Baertsch, Hans Sioutas, Constantinos Morgan, Todd E. Finch, Caleb E. Zlokovic, Berislav V. Mack, William J. Front Immunol Immunology Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations. Frontiers Media S.A. 2021-11-16 /pmc/articles/PMC8635097/ /pubmed/34868068 http://dx.doi.org/10.3389/fimmu.2021.785519 Text en Copyright © 2021 Huuskonen, Liu, Lamorie-Foote, Shkirkova, Connor, Patel, Montagne, Baertsch, Sioutas, Morgan, Finch, Zlokovic and Mack https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Huuskonen, Mikko T.
Liu, Qinghai
Lamorie-Foote, Krista
Shkirkova, Kristina
Connor, Michelle
Patel, Arati
Montagne, Axel
Baertsch, Hans
Sioutas, Constantinos
Morgan, Todd E.
Finch, Caleb E.
Zlokovic, Berislav V.
Mack, William J.
Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
title Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
title_full Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
title_fullStr Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
title_full_unstemmed Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
title_short Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
title_sort air pollution particulate matter amplifies white matter vascular pathology and demyelination caused by hypoperfusion
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635097/
https://www.ncbi.nlm.nih.gov/pubmed/34868068
http://dx.doi.org/10.3389/fimmu.2021.785519
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