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Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke

Stroke is one of the main causes of death and disability worldwide. Over the past decades, several animal models of focal cerebral ischemia have been developed allowing to investigate pathophysiological mechanisms underlying stroke progression. Despite intense preclinical research efforts, the need...

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Autores principales: Conti, Emilia, Carlini, Noemi, Piccardi, Benedetta, Allegra Mascaro, Anna Letizia, Pavone, Francesco Saverio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910575/
https://www.ncbi.nlm.nih.gov/pubmed/36650068
http://dx.doi.org/10.1523/ENEURO.0244-22.2022
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author Conti, Emilia
Carlini, Noemi
Piccardi, Benedetta
Allegra Mascaro, Anna Letizia
Pavone, Francesco Saverio
author_facet Conti, Emilia
Carlini, Noemi
Piccardi, Benedetta
Allegra Mascaro, Anna Letizia
Pavone, Francesco Saverio
author_sort Conti, Emilia
collection PubMed
description Stroke is one of the main causes of death and disability worldwide. Over the past decades, several animal models of focal cerebral ischemia have been developed allowing to investigate pathophysiological mechanisms underlying stroke progression. Despite intense preclinical research efforts, the need for noninvasive mouse models of vascular occlusion targeting the middle cerebral artery yet avoiding mechanical intervention is still pressing. Here, by applying the photothrombotic stroke model to the distal branch of the middle cerebral artery, we developed a novel strategy to induce a targeted occlusion of a large blood vessel in mice. This approach induces unilateral damage encompassing most of the dorsal cortex from the motor up to the visual regions 1 week after stroke. Pronounced limb dystonia one day after the damage is partially recovered after one week. Furthermore, we observe the insurgence of blood vessel leakage and edema formation in the peri-infarct area. Finally, this model elicits a notable inflammatory response revealed as a strong increase in astrocyte density and morphologic complexity in the perilesional region of the cortex compared with both other regions of the ipsilesional and contralesional hemispheres, and in sham-operated mice. To conclude, the stroke model we developed induces in mice the light-mediated occlusion of one of the main targets of human ischemic stroke, the middle cerebral artery, free from the limitations of commonly used preclinical models.
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spelling pubmed-99105752023-02-10 Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke Conti, Emilia Carlini, Noemi Piccardi, Benedetta Allegra Mascaro, Anna Letizia Pavone, Francesco Saverio eNeuro Research Article: Methods/New Tools Stroke is one of the main causes of death and disability worldwide. Over the past decades, several animal models of focal cerebral ischemia have been developed allowing to investigate pathophysiological mechanisms underlying stroke progression. Despite intense preclinical research efforts, the need for noninvasive mouse models of vascular occlusion targeting the middle cerebral artery yet avoiding mechanical intervention is still pressing. Here, by applying the photothrombotic stroke model to the distal branch of the middle cerebral artery, we developed a novel strategy to induce a targeted occlusion of a large blood vessel in mice. This approach induces unilateral damage encompassing most of the dorsal cortex from the motor up to the visual regions 1 week after stroke. Pronounced limb dystonia one day after the damage is partially recovered after one week. Furthermore, we observe the insurgence of blood vessel leakage and edema formation in the peri-infarct area. Finally, this model elicits a notable inflammatory response revealed as a strong increase in astrocyte density and morphologic complexity in the perilesional region of the cortex compared with both other regions of the ipsilesional and contralesional hemispheres, and in sham-operated mice. To conclude, the stroke model we developed induces in mice the light-mediated occlusion of one of the main targets of human ischemic stroke, the middle cerebral artery, free from the limitations of commonly used preclinical models. Society for Neuroscience 2023-02-07 /pmc/articles/PMC9910575/ /pubmed/36650068 http://dx.doi.org/10.1523/ENEURO.0244-22.2022 Text en Copyright © 2023 Conti et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: Methods/New Tools
Conti, Emilia
Carlini, Noemi
Piccardi, Benedetta
Allegra Mascaro, Anna Letizia
Pavone, Francesco Saverio
Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke
title Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke
title_full Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke
title_fullStr Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke
title_full_unstemmed Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke
title_short Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke
title_sort photothrombotic middle cerebral artery occlusion in mice: a novel model of ischemic stroke
topic Research Article: Methods/New Tools
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910575/
https://www.ncbi.nlm.nih.gov/pubmed/36650068
http://dx.doi.org/10.1523/ENEURO.0244-22.2022
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