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Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation
Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CV...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9474533/ https://www.ncbi.nlm.nih.gov/pubmed/36104366 http://dx.doi.org/10.1038/s41598-022-19113-8 |
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author | Chiarelli, Antonio Maria Villani, Alessandro Mascali, Daniele Petsas, Nikolaos Biondetti, Emma Caporale, Alessandra Digiovanni, Anna Grasso, Eleonora Agata Ajdinaj, Paola D’Apolito, Maria Rispoli, Marianna Gabriella Sensi, Stefano Murphy, Kevin Pozzilli, Carlo Wise, Richard G. Tomassini, Valentina |
author_facet | Chiarelli, Antonio Maria Villani, Alessandro Mascali, Daniele Petsas, Nikolaos Biondetti, Emma Caporale, Alessandra Digiovanni, Anna Grasso, Eleonora Agata Ajdinaj, Paola D’Apolito, Maria Rispoli, Marianna Gabriella Sensi, Stefano Murphy, Kevin Pozzilli, Carlo Wise, Richard G. Tomassini, Valentina |
author_sort | Chiarelli, Antonio Maria |
collection | PubMed |
description | Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVR(GM) and CVR(WM), respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVR(GM) (p = 0.04) and CVR(WM) (p = 0.02) compared to HC. In patients, a lower pre-treatment CVR(GM) was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVR(GM) (p = 0.02) and CVR(WM) (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = − 0.58, p = 0.005; WM: r = − 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = − 0.48, p = 0.02, WM: r = − 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring. |
format | Online Article Text |
id | pubmed-9474533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94745332022-09-16 Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation Chiarelli, Antonio Maria Villani, Alessandro Mascali, Daniele Petsas, Nikolaos Biondetti, Emma Caporale, Alessandra Digiovanni, Anna Grasso, Eleonora Agata Ajdinaj, Paola D’Apolito, Maria Rispoli, Marianna Gabriella Sensi, Stefano Murphy, Kevin Pozzilli, Carlo Wise, Richard G. Tomassini, Valentina Sci Rep Article Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVR(GM) and CVR(WM), respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVR(GM) (p = 0.04) and CVR(WM) (p = 0.02) compared to HC. In patients, a lower pre-treatment CVR(GM) was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVR(GM) (p = 0.02) and CVR(WM) (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = − 0.58, p = 0.005; WM: r = − 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = − 0.48, p = 0.02, WM: r = − 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring. Nature Publishing Group UK 2022-09-14 /pmc/articles/PMC9474533/ /pubmed/36104366 http://dx.doi.org/10.1038/s41598-022-19113-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chiarelli, Antonio Maria Villani, Alessandro Mascali, Daniele Petsas, Nikolaos Biondetti, Emma Caporale, Alessandra Digiovanni, Anna Grasso, Eleonora Agata Ajdinaj, Paola D’Apolito, Maria Rispoli, Marianna Gabriella Sensi, Stefano Murphy, Kevin Pozzilli, Carlo Wise, Richard G. Tomassini, Valentina Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation |
title | Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation |
title_full | Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation |
title_fullStr | Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation |
title_full_unstemmed | Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation |
title_short | Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation |
title_sort | cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9474533/ https://www.ncbi.nlm.nih.gov/pubmed/36104366 http://dx.doi.org/10.1038/s41598-022-19113-8 |
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