Cargando…

Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation

Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with...

Descripción completa

Detalles Bibliográficos
Autores principales: Gama Sosa, Miguel A., De Gasperi, Rita, Pryor, Dylan, Perez Garcia, Georgina S., Perez, Gissel M., Abutarboush, Rania, Kawoos, Usmah, Hogg, Seth, Ache, Benjamin, Janssen, William G., Sowa, Allison, Tetreault, Timothy, Cook, David G., Tappan, Susan J., Gandy, Sam, Hof, Patrick R., Ahlers, Stephen T., Elder, Gregory A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518227/
https://www.ncbi.nlm.nih.gov/pubmed/34654480
http://dx.doi.org/10.1186/s40478-021-01269-5
_version_ 1784584178086445056
author Gama Sosa, Miguel A.
De Gasperi, Rita
Pryor, Dylan
Perez Garcia, Georgina S.
Perez, Gissel M.
Abutarboush, Rania
Kawoos, Usmah
Hogg, Seth
Ache, Benjamin
Janssen, William G.
Sowa, Allison
Tetreault, Timothy
Cook, David G.
Tappan, Susan J.
Gandy, Sam
Hof, Patrick R.
Ahlers, Stephen T.
Elder, Gregory A.
author_facet Gama Sosa, Miguel A.
De Gasperi, Rita
Pryor, Dylan
Perez Garcia, Georgina S.
Perez, Gissel M.
Abutarboush, Rania
Kawoos, Usmah
Hogg, Seth
Ache, Benjamin
Janssen, William G.
Sowa, Allison
Tetreault, Timothy
Cook, David G.
Tappan, Susan J.
Gandy, Sam
Hof, Patrick R.
Ahlers, Stephen T.
Elder, Gregory A.
author_sort Gama Sosa, Miguel A.
collection PubMed
description Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury.
format Online
Article
Text
id pubmed-8518227
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-85182272021-10-20 Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation Gama Sosa, Miguel A. De Gasperi, Rita Pryor, Dylan Perez Garcia, Georgina S. Perez, Gissel M. Abutarboush, Rania Kawoos, Usmah Hogg, Seth Ache, Benjamin Janssen, William G. Sowa, Allison Tetreault, Timothy Cook, David G. Tappan, Susan J. Gandy, Sam Hof, Patrick R. Ahlers, Stephen T. Elder, Gregory A. Acta Neuropathol Commun Research Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury. BioMed Central 2021-10-15 /pmc/articles/PMC8518227/ /pubmed/34654480 http://dx.doi.org/10.1186/s40478-021-01269-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Gama Sosa, Miguel A.
De Gasperi, Rita
Pryor, Dylan
Perez Garcia, Georgina S.
Perez, Gissel M.
Abutarboush, Rania
Kawoos, Usmah
Hogg, Seth
Ache, Benjamin
Janssen, William G.
Sowa, Allison
Tetreault, Timothy
Cook, David G.
Tappan, Susan J.
Gandy, Sam
Hof, Patrick R.
Ahlers, Stephen T.
Elder, Gregory A.
Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
title Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
title_full Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
title_fullStr Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
title_full_unstemmed Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
title_short Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
title_sort low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518227/
https://www.ncbi.nlm.nih.gov/pubmed/34654480
http://dx.doi.org/10.1186/s40478-021-01269-5
work_keys_str_mv AT gamasosamiguela lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT degasperirita lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT pryordylan lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT perezgarciageorginas lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT perezgisselm lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT abutarboushrania lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT kawoosusmah lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT hoggseth lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT achebenjamin lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT janssenwilliamg lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT sowaallison lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT tetreaulttimothy lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT cookdavidg lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT tappansusanj lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT gandysam lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT hofpatrickr lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT ahlersstephent lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation
AT eldergregorya lowlevelblastexposureinduceschronicvascularremodelingperivascularastrocyticdegenerationandvascularassociatedneuroinflammation