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Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia

In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization....

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Autores principales: Krueger, Martin, Mages, Bianca, Hobusch, Constance, Michalski, Dominik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369548/
https://www.ncbi.nlm.nih.gov/pubmed/30744693
http://dx.doi.org/10.1186/s40478-019-0671-0
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author Krueger, Martin
Mages, Bianca
Hobusch, Constance
Michalski, Dominik
author_facet Krueger, Martin
Mages, Bianca
Hobusch, Constance
Michalski, Dominik
author_sort Krueger, Martin
collection PubMed
description In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization. Therefore, the present study was aimed to investigate early vascular alterations from 30 min to 4 h after experimental middle cerebral artery occlusion (MCAO) in mice. Here, an extravasation of the permeability marker FITC-albumin was detectable in animals 2 and 4 h after MCAO. Thereby, BBB breakdown correlated with alterations of the endothelial surface, indicated by a discontinuous isolectin-B4 staining, while tight junction strands remained detectable using electron and immunofluorescence microscopy. Noteworthy, already 30 min after MCAO, up to 60% of the ischemia-affected vessels showed an endothelial edema, paralleled by edematous astrocytic endfeet, clearly preceding FITC-albumin extravasation. With increasing ischemic periods, scores of vascular damage significantly increased with up to 60% of the striatal vessels showing loss of endothelial integrity. Remarkably, comparison of permanent and transient ischemia did not provide significant differences 4 h after ischemia induction. As these degenerations also involved penumbral areas of potentially salvageable tissue, adjuvant approaches of endothelial protection may help to reduce the vasogenic edema after ischemic stroke. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-019-0671-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-63695482019-02-21 Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia Krueger, Martin Mages, Bianca Hobusch, Constance Michalski, Dominik Acta Neuropathol Commun Research In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization. Therefore, the present study was aimed to investigate early vascular alterations from 30 min to 4 h after experimental middle cerebral artery occlusion (MCAO) in mice. Here, an extravasation of the permeability marker FITC-albumin was detectable in animals 2 and 4 h after MCAO. Thereby, BBB breakdown correlated with alterations of the endothelial surface, indicated by a discontinuous isolectin-B4 staining, while tight junction strands remained detectable using electron and immunofluorescence microscopy. Noteworthy, already 30 min after MCAO, up to 60% of the ischemia-affected vessels showed an endothelial edema, paralleled by edematous astrocytic endfeet, clearly preceding FITC-albumin extravasation. With increasing ischemic periods, scores of vascular damage significantly increased with up to 60% of the striatal vessels showing loss of endothelial integrity. Remarkably, comparison of permanent and transient ischemia did not provide significant differences 4 h after ischemia induction. As these degenerations also involved penumbral areas of potentially salvageable tissue, adjuvant approaches of endothelial protection may help to reduce the vasogenic edema after ischemic stroke. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-019-0671-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-11 /pmc/articles/PMC6369548/ /pubmed/30744693 http://dx.doi.org/10.1186/s40478-019-0671-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Krueger, Martin
Mages, Bianca
Hobusch, Constance
Michalski, Dominik
Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia
title Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia
title_full Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia
title_fullStr Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia
title_full_unstemmed Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia
title_short Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia
title_sort endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369548/
https://www.ncbi.nlm.nih.gov/pubmed/30744693
http://dx.doi.org/10.1186/s40478-019-0671-0
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