dc.contributor.author | Joya, Ana | |
dc.contributor.author | Ardaya Franco, María Isabel | |
dc.contributor.author | Montilla López, Alejandro | |
dc.contributor.author | Garbizu, Maider | |
dc.contributor.author | Plaza García, Sandra | |
dc.contributor.author | Gómez Vallejo, Vanessa | |
dc.contributor.author | Padró, Daniel | |
dc.contributor.author | Gutiérrez Martín, Juan José | |
dc.contributor.author | Ríos, Xabier | |
dc.contributor.author | Ramos Cabrer, Pedro | |
dc.contributor.author | Cossío Arrieta, Unai | |
dc.contributor.author | Pulagam, Krishna Reddy | |
dc.contributor.author | Higuchi, Makoto | |
dc.contributor.author | Domercq García, María | |
dc.contributor.author | Cavaliere, Fabio | |
dc.contributor.author | Matute Almau, Carlos José | |
dc.contributor.author | Llop Roig, Jordi | |
dc.contributor.author | Martín Muñoz, Abraham | |
dc.date.accessioned | 2021-02-24T08:37:17Z | |
dc.date.available | 2021-02-24T08:37:17Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Theranostics 11(1) : 410-425 (2021) | es_ES |
dc.identifier.issn | 1838-7640 | |
dc.identifier.uri | http://hdl.handle.net/10810/50306 | |
dc.description.abstract | Adenosine A(l) receptors (A(l)ARs) are promising imaging biomarkers and targets for the treatment of stroke. Nevertheless, the role of A(l)ARs on ischemic damage and its subsequent neuroinflammatory response has been scarcely explored so far.
Methods: In this study, the expression of A(1)ARs after transient middle cerebral artery occlusion (MCAO) was evaluated by positron emission tomography (PET) with [F-18]CPFPX and immunohistochemistry (IHC). In addition, the role of AIARs on stroke inflammation using pharmacological modulation was assessed with magnetic resonance imaging (MRI), PET imaging with [F-18]DPA-714 (TSPO) and [F-18]FLT (cellular proliferation), as well as IHC and neurofunctional studies.
Results: In the ischemic territory, [F-18]CPFPX signal and IHC showed the overexpression of A(l)ARs in microglia and infiltrated leukocytes after cerebral ischemia. Ischemic rats treated with the AAR agonist ENBA showed a significant decrease in both [F-18]DPA-714 and [F-18]FLT signal intensities at day 7 after cerebral ischemia, a feature that was confirmed by IHC results. Besides, the activation of A(l)AR promoted the reduction of the brain lesion, as measured with T2W-MRI, and the improvement of neurological outcome including motor, sensory and reflex responses. These results show for the first time the in vivo PET imaging of A(l)AR expression after cerebral ischemia in rats and the application of [F-18]FLT to evaluate glial proliferation in response to treatment.
Conclusion: Notably, these data provide evidence for A(l)AR playing a key role in the control of both the activation of resident glia and the de novo proliferation of microglia and macrophages after experimental stroke in rats. | es_ES |
dc.description.sponsorship | The authors would like to thank A. Leukona 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-201722412, SAF2016-75292-R, SAF2017-87670-R and 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). Juan Jose Gutierrez acknowledges funding from Euskampus Fundazioa. Jordi Llop also acknowledges The Spanish Ministry of Economy and Competitiveness (Grant CTQ2017-87637-R). 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). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Ivyspring International Publisher | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/RYC-201722412 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2016-75292-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-87670-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/PID2019-107989RB-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/CTQ2017-87637-R | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | [F-18]CPFPX | es_ES |
dc.subject | [F-18]DPA-714 | es_ES |
dc.subject | [F-18]FLT | es_ES |
dc.subject | PET | es_ES |
dc.subject | A(1)AR | es_ES |
dc.subject | cerebral ischemia | es_ES |
dc.subject | MRI | es_ES |
dc.subject | neuroinflammation | es_ES |
dc.subject | A(1) receptors | es_ES |
dc.subject | brain | es_ES |
dc.subject | proliferation | es_ES |
dc.subject | inflammation | es_ES |
dc.subject | inhibition | es_ES |
dc.subject | antagonist | es_ES |
dc.subject | activation | es_ES |
dc.title | In vivo multimodal imaging of adenosine A1 receptors in neuroinflammation after experimental stroke | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.thno.org/v11p0410.htm | es_ES |
dc.identifier.doi | 10.7150/thno.51046 | |
dc.departamentoes | Neurociencias | es_ES |
dc.departamentoes | Química física | es_ES |
dc.departamentoeu | Kimika fisikoa | es_ES |
dc.departamentoeu | Neurozientziak | es_ES |