In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats

In vivopositron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far.In vivoandex vivoassessment of gliogenesis a...

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Autores: Ardaya Franco, María Isabel, Joya, Ana, Padró, Daniel, Plaza García, Sandra, Gómez Vallejo, Vanessa, Sánchez, Mercedes, Garbizu, Maider, Cossío Arrieta, Unai, Matute Almau, Carlos José, Cavaliere, Fabio, Llop Roig, Jordi, Martín Muñoz, Abraham
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/49817
Acceso en línea:http://hdl.handle.net/10810/49817
Access Level:acceso abierto
Palabra clave:cerebral ischemia
PET
[F-18]FLT
gliogenesis
glia
cell-proliferation
brain inflammation
receptor
mechanisms
oncology
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spelling In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in RatsArdaya Franco, María IsabelJoya, AnaPadró, DanielPlaza García, SandraGómez Vallejo, VanessaSánchez, MercedesGarbizu, MaiderCossío Arrieta, UnaiMatute Almau, Carlos JoséCavaliere, FabioLlop Roig, JordiMartín Muñoz, Abrahamcerebral ischemiaPET[F-18]FLTgliogenesisgliacell-proliferationbrain inflammationreceptormechanismsoncologyIn vivopositron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far.In vivoandex vivoassessment of gliogenesis after transient middle cerebral artery occlusion (MCAO) in rats was carried out using PET imaging with the marker of cell proliferation 3 '-Deoxy-3 '-[18F] fluorothymidine ([F-18]FLT), magnetic resonance imaging (MRI) and fluorescence immunohistochemistry. MRI-T2W studies showed the presence of the brain infarction at 24 h after MCAO affecting cerebral cortex and striatum.In vivoPET imaging showed a significant increase in [F-18]FLT uptake in the ischemic territory at day 7 followed by a progressive decline from day 14 to day 28 after ischemia onset. In addition, immunohistochemistry studies using Ki67, CD11b, and GFAP to evaluate proliferation of microglia and astrocytes confirmed the PET findings showing the increase of glial proliferation at day 7 after ischemia followed by decrease later on. Hence, these results show that [F-18]FLT provides accurate quantitative information on the time course of glial proliferation in experimental stroke. Finally, this novel brain imaging method might guide on the imaging evaluation of the role of gliogenesis after stroke.The authors would like to thank A. Leukona, X. Rios-Anglada, and V. Salinas for technical support in the radiosynthesis. This study was funded by grants from the Spanish Ministry of Education and Science/FEDER RYC-2017-22412, SAF2016-75292-R, PID2019-107989RB-I00, the Basque Government (IT1203/19, BIO18/IC/006) and CIBERNED. Maria Ardaya holds a fellowship from the University of Pais Vasco. Ana Joya acknowledges funding from Fundacio La Marato de TV3 (17/C/2017). Part of the work has been performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (Grant No. MDM-2017-0720).Frontiers Media202120212020info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/49817reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MCIU/RYC-2017-22412/info:eu-repo/grantAgreement/MCIU/SAF2016-75292-R/info:eu-repo/grantAgreement/MCIU/PID2019-107989RB-I00/https://www.frontiersin.org/articles/10.3389/fnins.2020.00793/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/2020 Ardaya, Joya, Padro, Plaza-García, Gómez-Vallejo, Sánchez, Garbizu, Cossío, Matute, Cavaliere, Llop and Martín. 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.Atribución 3.0 Españaoai:addi.ehu.eus:10810/498172026-06-18T09:23:17Z
dc.title.none.fl_str_mv In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
title In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
spellingShingle In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
Ardaya Franco, María Isabel
cerebral ischemia
PET
[F-18]FLT
gliogenesis
glia
cell-proliferation
brain inflammation
receptor
mechanisms
oncology
title_short In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
title_full In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
title_fullStr In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
title_full_unstemmed In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
title_sort In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats
dc.creator.none.fl_str_mv Ardaya Franco, María Isabel
Joya, Ana
Padró, Daniel
Plaza García, Sandra
Gómez Vallejo, Vanessa
Sánchez, Mercedes
Garbizu, Maider
Cossío Arrieta, Unai
Matute Almau, Carlos José
Cavaliere, Fabio
Llop Roig, Jordi
Martín Muñoz, Abraham
author Ardaya Franco, María Isabel
author_facet Ardaya Franco, María Isabel
Joya, Ana
Padró, Daniel
Plaza García, Sandra
Gómez Vallejo, Vanessa
Sánchez, Mercedes
Garbizu, Maider
Cossío Arrieta, Unai
Matute Almau, Carlos José
Cavaliere, Fabio
Llop Roig, Jordi
Martín Muñoz, Abraham
author_role author
author2 Joya, Ana
Padró, Daniel
Plaza García, Sandra
Gómez Vallejo, Vanessa
Sánchez, Mercedes
Garbizu, Maider
Cossío Arrieta, Unai
Matute Almau, Carlos José
Cavaliere, Fabio
Llop Roig, Jordi
Martín Muñoz, Abraham
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv cerebral ischemia
PET
[F-18]FLT
gliogenesis
glia
cell-proliferation
brain inflammation
receptor
mechanisms
oncology
topic cerebral ischemia
PET
[F-18]FLT
gliogenesis
glia
cell-proliferation
brain inflammation
receptor
mechanisms
oncology
description In vivopositron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far.In vivoandex vivoassessment of gliogenesis after transient middle cerebral artery occlusion (MCAO) in rats was carried out using PET imaging with the marker of cell proliferation 3 '-Deoxy-3 '-[18F] fluorothymidine ([F-18]FLT), magnetic resonance imaging (MRI) and fluorescence immunohistochemistry. MRI-T2W studies showed the presence of the brain infarction at 24 h after MCAO affecting cerebral cortex and striatum.In vivoPET imaging showed a significant increase in [F-18]FLT uptake in the ischemic territory at day 7 followed by a progressive decline from day 14 to day 28 after ischemia onset. In addition, immunohistochemistry studies using Ki67, CD11b, and GFAP to evaluate proliferation of microglia and astrocytes confirmed the PET findings showing the increase of glial proliferation at day 7 after ischemia followed by decrease later on. Hence, these results show that [F-18]FLT provides accurate quantitative information on the time course of glial proliferation in experimental stroke. Finally, this novel brain imaging method might guide on the imaging evaluation of the role of gliogenesis after stroke.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/49817
url http://hdl.handle.net/10810/49817
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MCIU/RYC-2017-22412/
info:eu-repo/grantAgreement/MCIU/SAF2016-75292-R/
info:eu-repo/grantAgreement/MCIU/PID2019-107989RB-I00/
https://www.frontiersin.org/articles/10.3389/fnins.2020.00793/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
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