Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice

Detalhes bibliográficos
Autor(a) principal: Sousa, Larissa Fonseca da Cunha
Data de Publicação: 2013
Outros Autores: Coelho, Fernanda Matos, Rodrigues, David Henrique, Campos, Alline Cristina, Barcelos, Luciola da Silva, Teixeira, Mauro Martins, Rachid, Milene Alvarenga, Teixeira, Antonio Lucio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Clinics
Texto Completo: https://www.revistas.usp.br/clinics/article/view/72139
Resumo: OBJECTIVE: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice. METHODS: C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA. RESULTS: Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment. CONCLUSIONS: Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.
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spelling Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in miceCerebral IschemiaNeutrophilsReparixinCXCR1/CXCR2 ReceptorsOBJECTIVE: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice. METHODS: C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA. RESULTS: Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment. CONCLUSIONS: Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2013-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/7213910.1590/clin.v68i3.72139Clinics; Vol. 68 No. 3 (2013); 391-394Clinics; v. 68 n. 3 (2013); 391-394Clinics; Vol. 68 Núm. 3 (2013); 391-3941980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/72139/75374Sousa, Larissa Fonseca da CunhaCoelho, Fernanda MatosRodrigues, David HenriqueCampos, Alline CristinaBarcelos, Luciola da SilvaTeixeira, Mauro MartinsRachid, Milene AlvarengaTeixeira, Antonio Lucioinfo:eu-repo/semantics/openAccess2014-01-28T17:05:37Zoai:revistas.usp.br:article/72139Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2014-01-28T17:05:37Clinics - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
title Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
spellingShingle Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
Sousa, Larissa Fonseca da Cunha
Cerebral Ischemia
Neutrophils
Reparixin
CXCR1/CXCR2 Receptors
title_short Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
title_full Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
title_fullStr Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
title_full_unstemmed Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
title_sort Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice
author Sousa, Larissa Fonseca da Cunha
author_facet Sousa, Larissa Fonseca da Cunha
Coelho, Fernanda Matos
Rodrigues, David Henrique
Campos, Alline Cristina
Barcelos, Luciola da Silva
Teixeira, Mauro Martins
Rachid, Milene Alvarenga
Teixeira, Antonio Lucio
author_role author
author2 Coelho, Fernanda Matos
Rodrigues, David Henrique
Campos, Alline Cristina
Barcelos, Luciola da Silva
Teixeira, Mauro Martins
Rachid, Milene Alvarenga
Teixeira, Antonio Lucio
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Sousa, Larissa Fonseca da Cunha
Coelho, Fernanda Matos
Rodrigues, David Henrique
Campos, Alline Cristina
Barcelos, Luciola da Silva
Teixeira, Mauro Martins
Rachid, Milene Alvarenga
Teixeira, Antonio Lucio
dc.subject.por.fl_str_mv Cerebral Ischemia
Neutrophils
Reparixin
CXCR1/CXCR2 Receptors
topic Cerebral Ischemia
Neutrophils
Reparixin
CXCR1/CXCR2 Receptors
description OBJECTIVE: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice. METHODS: C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA. RESULTS: Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment. CONCLUSIONS: Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.
publishDate 2013
dc.date.none.fl_str_mv 2013-01-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/clinics/article/view/72139
10.1590/clin.v68i3.72139
url https://www.revistas.usp.br/clinics/article/view/72139
identifier_str_mv 10.1590/clin.v68i3.72139
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/clinics/article/view/72139/75374
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
dc.source.none.fl_str_mv Clinics; Vol. 68 No. 3 (2013); 391-394
Clinics; v. 68 n. 3 (2013); 391-394
Clinics; Vol. 68 Núm. 3 (2013); 391-394
1980-5322
1807-5932
reponame:Clinics
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Clinics
collection Clinics
repository.name.fl_str_mv Clinics - Universidade de São Paulo (USP)
repository.mail.fl_str_mv ||clinics@hc.fm.usp.br
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