Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography
Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovascul...
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Published in | Frontiers in aging neuroscience Vol. 12; p. 585218 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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20.10.2020
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Abstract | Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide
whole-brain imaging of the cerebrovasculature in aging C57BL/6 mice longitudinally, contrast-enhanced magnetic resonance angiography (CE-MRA) was employed using a house-made gadolinium-bearing micellar blood pool agent. Enhancement in the vascular space permitted quantification of the detectable, or apparent, cerebral blood volume (aCBV), which was analyzed over 2 years of aging and compared to histological analysis of the cerebrovascular density. A significant loss in the aCBV was detected by CE-MRA over the aging period. Histological analysis
vessel-probing immunohistochemistry confirmed a significant loss in the cerebrovascular density over the same 2-year aging period, validating the CE-MRA findings. While these techniques use widely different methods of assessment and spatial resolutions, their comparable findings in detected vascular loss corroborate the growing body of literature describing vascular rarefaction aging. These findings suggest that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents. |
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AbstractList | Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide in vivo whole-brain imaging of the cerebrovasculature in aging C57BL/6 mice longitudinally, contrast-enhanced magnetic resonance angiography (CE-MRA) was employed using a house-made gadolinium-bearing micellar blood pool agent. Enhancement in the vascular space permitted quantification of the detectable, or apparent, cerebral blood volume (aCBV), which was analyzed over 2 years of aging and compared to histological analysis of the cerebrovascular density. A significant loss in the aCBV was detected by CE-MRA over the aging period. Histological analysis via vessel-probing immunohistochemistry confirmed a significant loss in the cerebrovascular density over the same 2-year aging period, validating the CE-MRA findings. While these techniques use widely different methods of assessment and spatial resolutions, their comparable findings in detected vascular loss corroborate the growing body of literature describing vascular rarefaction aging. These findings suggest that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents. Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide whole-brain imaging of the cerebrovasculature in aging C57BL/6 mice longitudinally, contrast-enhanced magnetic resonance angiography (CE-MRA) was employed using a house-made gadolinium-bearing micellar blood pool agent. Enhancement in the vascular space permitted quantification of the detectable, or apparent, cerebral blood volume (aCBV), which was analyzed over 2 years of aging and compared to histological analysis of the cerebrovascular density. A significant loss in the aCBV was detected by CE-MRA over the aging period. Histological analysis vessel-probing immunohistochemistry confirmed a significant loss in the cerebrovascular density over the same 2-year aging period, validating the CE-MRA findings. While these techniques use widely different methods of assessment and spatial resolutions, their comparable findings in detected vascular loss corroborate the growing body of literature describing vascular rarefaction aging. These findings suggest that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents. Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide in vivo whole-brain imaging of the cerebrovasculature in aging C57BL/6 mice longitudinally, contrast-enhanced magnetic resonance angiography (CE-MRA) was employed using a house-made gadolinium-bearing micellar blood pool agent. Enhancement in the vascular space permitted quantification of the detectable, or apparent, cerebral blood volume (aCBV), which was analyzed over 2 years of aging and compared to histological analysis of the cerebrovascular density. A significant loss in the aCBV was detected by CE-MRA over the aging period. Histological analysis via vessel-probing immunohistochemistry confirmed a significant loss in the cerebrovascular density over the same 2-year aging period, validating the CE-MRA findings. While these techniques use widely different methods of assessment and spatial resolutions, their comparable findings in detected vascular loss corroborate the growing body of literature describing vascular rarefaction aging. These findings suggest that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents. Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization and quantification of the global murine cerebrovasculature is necessary in establishing the baseline changes that occur with aging. In order to provide in vivo whole brain imaging of the cerebrovasculature in aging C57BL/6 mice longitudinally, contrast-enhanced magnetic resonance angiography (CE-MRA) was employed using a house-made gadolinium-bearing micellar blood pool agent. Enhancement in the vascular space permitted quantification of the detectable, or apparent, cerebral blood volume (aCBV), which was analyzed over 2 years of aging and compared to histological analysis of the cerebrovascular density. A significant loss in the aCBV was detected by CE-MRA over the aging period. Histological analysis via vessel-probing immunohistochemistry confirmed a significant loss in the cerebrovascular density over the same 2-year aging period, validating the CE-MRA findings. While these techniques use widely different methods of assessment and spatial resolutions, their similarity in detected vascular loss corroborates the growing body of literature describing vascular rarefaction in aging and suggests that such age-dependent changes can contribute to cerebrovascular and neurodegenerative diseases, which are modeled using wild-type and transgenic laboratory rodents. |
Author | Hoang, Dung Minh Chiriboga, Luis A Wisniewski, Thomas Wadghiri, Youssef Z Sadowski, Martin J Hill, Lindsay K |
AuthorAffiliation | 5 Department of Pathology, NYU Grossman School of Medicine , New York, NY , United States 4 Department of Biomedical Engineering, SUNY Downstate Medical Center , Brooklyn, NY , United States 8 Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine , New York, NY , United States 2 Department of Radiology, Center for Advanced Imaging Innovation and Research (CAI2R), NYU Grossman School of Medicine , New York, NY , United States 7 Department of Psychiatry, NYU Grossman School of Medicine , New York, NY , United States 6 Department of Neurology, NYU Grossman School of Medicine , New York, NY , United States 1 Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering , Brooklyn, NY , United States 3 Department of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine , New York, NY , United States |
AuthorAffiliation_xml | – name: 1 Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering , Brooklyn, NY , United States – name: 2 Department of Radiology, Center for Advanced Imaging Innovation and Research (CAI2R), NYU Grossman School of Medicine , New York, NY , United States – name: 4 Department of Biomedical Engineering, SUNY Downstate Medical Center , Brooklyn, NY , United States – name: 7 Department of Psychiatry, NYU Grossman School of Medicine , New York, NY , United States – name: 6 Department of Neurology, NYU Grossman School of Medicine , New York, NY , United States – name: 8 Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine , New York, NY , United States – name: 5 Department of Pathology, NYU Grossman School of Medicine , New York, NY , United States – name: 3 Department of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine , New York, NY , United States |
Author_xml | – sequence: 1 givenname: Lindsay K surname: Hill fullname: Hill, Lindsay K organization: Department of Biomedical Engineering, SUNY Downstate Medical Center, Brooklyn, NY, United States – sequence: 2 givenname: Dung Minh surname: Hoang fullname: Hoang, Dung Minh organization: Department of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United States – sequence: 3 givenname: Luis A surname: Chiriboga fullname: Chiriboga, Luis A organization: Department of Pathology, NYU Grossman School of Medicine, New York, NY, United States – sequence: 4 givenname: Thomas surname: Wisniewski fullname: Wisniewski, Thomas organization: Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, United States – sequence: 5 givenname: Martin J surname: Sadowski fullname: Sadowski, Martin J organization: Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, United States – sequence: 6 givenname: Youssef Z surname: Wadghiri fullname: Wadghiri, Youssef Z organization: Department of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United States |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33192479$$D View this record in MEDLINE/PubMed |
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ContentType | Journal Article |
Copyright | Copyright © 2020 Hill, Hoang, Chiriboga, Wisniewski, Sadowski and Wadghiri. 2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2020 Hill, Hoang, Chiriboga, Wisniewski, Sadowski and Wadghiri. 2020 Hill, Hoang, Chiriboga, Wisniewski, Sadowski and Wadghiri |
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Keywords | cerebral blood volume (CBV) magnetic resonance (MR) angiography mouse brain aging rarefaction MRI blood pool agent |
Language | English |
License | Copyright © 2020 Hill, Hoang, Chiriboga, Wisniewski, Sadowski and Wadghiri. 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. |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ORCID: Lindsay K. Hill orcid.org/0000-0002-1833-8574 Dung Minh Hoang orcid.org/0000-0001-7613-7167 Luis A. Chiriboga orcid.org/0000-0002-2028-6873 Thomas Wisniewski orcid.org/0000-0002-3379-8966 Martin J. Sadowski orcid.org/0000-0002-3830-1779 Youssef Z. Wadghiri orcid.org/0000-0001-7175-9397 Reviewed by: Zoltan I. Ungvari, University of Oklahoma Health Sciences Center, United States; Patrizia Giannoni, University of Nîmes, France Edited by: Shuo Wang, Capital Medical University, China |
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Snippet | Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in... Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats and, more recently, mice in... |
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SubjectTerms | Age Aging Angiography Blood blood pool agent Brain Cerebral blood flow cerebral blood volume (CBV) Gadolinium Immunohistochemistry Laboratory animals Lipids magnetic resonance (MR) angiography Medical imaging Microscopy Microvasculature mouse brain aging MRI Neurodegenerative diseases Neuroimaging Neuroscience Polyethylene glycol rarefaction Vascular diseases |
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Title | Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography |
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