Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2012 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/16892 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. |
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Reis, Patricia AlvesEstato, VanessaSilva, Tathiany I. dad'Avila, Joana C.Siqueira, Luciana D.Assis, Edson F.Bozza, Patrícia T.Bozza, Fernando A.Tibiriça, Eduardo V.Zimmerman, Guy A.Faria Neto, Hugo C. Castro2017-01-18T14:06:20Z2017-01-18T14:06:20Z2012REIS, Patricia Alves et al. Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria. Plos Pathogens, v. 8, n. 12, p. 1- 13, Dec. 2012.1553-7366https://www.arca.fiocruz.br/handle/icict/1689210.1371/journal.ppat.10030991553-7374engPublic Library of ScienceMalária cerebralEstatinaTratamentoNeuroinflamaçãoPrevençãoDanos cognitivosCerebral MalariaStatinTreatmentNeuroinflammationPrevent Cognitive ImpairmentStatins decrease neuroinflammation and prevent cognitive impairment after cerebral malariainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.University of Utah School of Medicine. Department of Internal Medicine. Salt Lake City, Utah, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Cerebral malaria (CM) is the most severe manifestation of Plasmodium falciparum infection in children and non-immune adults. Previous work has documented a persistent cognitive impairment in children who survive an episode of CM that is mimicked in animal models of the disease. Potential therapeutic interventions for this complication have not been investigated, and are urgently needed. HMG-CoA reductase inhibitors (statins) are widely prescribed for cardiovascular diseases. In addition to their effects on the inhibition of cholesterol synthesis, statins have pleiotropic immunomodulatory activities. Here we tested if statins would prevent cognitive impairment in a murine model of cerebral malaria. Six days after infection with Plasmodium berghei ANKA (PbA) mice displayed clear signs of CM and were treated with chloroquine, or chloroquine and lovastatin. Intravital examination of pial vessels of infected animals demonstrated a decrease in functional capillary density and an increase in rolling and adhesion of leukocytes to inflamed endothelium that were reversed by treatment with lovastatin. In addition, oedema, ICAM-1, and CD11b mRNA levels were reduced in lovastatin-treated PbA-infected mice brains. Moreover, HMOX-1 mRNA levels are enhanced in lovastatin-treated healthy and infected brains. Oxidative stress and key inflammatory chemokines and cytokines were reduced to non-infected control levels in animals treated with lovastatin. Fifteen days post-infection cognitive dysfunction was detected by a battery of cognition tests in animals rescued from CM by chloroquine treatment. In contrast, it was absent in animals treated with lovastatin and chloroquine. The outcome was similar in experimental bacterial sepsis, suggesting that statins have neuroprotective effects in severe infectious syndromes in addition to CM. Statin treatment prevents neuroinflammation and blood brain barrier dysfunction in experimental CM and related conditions that are associated with cognitive sequelae, and may be a valuable adjuvant therapeutic agent for prevention of cognitive impairment in patients surviving an episode of CM.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/16892/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALpatricia_reis_etal_IOC_2012.pdfpatricia_reis_etal_IOC_2012.pdfapplication/pdf1311065https://www.arca.fiocruz.br/bitstream/icict/16892/2/patricia_reis_etal_IOC_2012.pdf4e9c37a7d11c22bd2bc95730f7e322c2MD52TEXTpatricia_reis_etal_IOC_2012.pdf.txtpatricia_reis_etal_IOC_2012.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria |
| title |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria |
| spellingShingle |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria Reis, Patricia Alves Malária cerebral Estatina Tratamento Neuroinflamação Prevenção Danos cognitivos Cerebral Malaria Statin Treatment Neuroinflammation Prevent Cognitive Impairment |
| title_short |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria |
| title_full |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria |
| title_fullStr |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria |
| title_full_unstemmed |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria |
| title_sort |
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria |
| author |
Reis, Patricia Alves |
| author_facet |
Reis, Patricia Alves Estato, Vanessa Silva, Tathiany I. da d'Avila, Joana C. Siqueira, Luciana D. Assis, Edson F. Bozza, Patrícia T. Bozza, Fernando A. Tibiriça, Eduardo V. Zimmerman, Guy A. Faria Neto, Hugo C. Castro |
| author_role |
author |
| author2 |
Estato, Vanessa Silva, Tathiany I. da d'Avila, Joana C. Siqueira, Luciana D. Assis, Edson F. Bozza, Patrícia T. Bozza, Fernando A. Tibiriça, Eduardo V. Zimmerman, Guy A. Faria Neto, Hugo C. Castro |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Reis, Patricia Alves Estato, Vanessa Silva, Tathiany I. da d'Avila, Joana C. Siqueira, Luciana D. Assis, Edson F. Bozza, Patrícia T. Bozza, Fernando A. Tibiriça, Eduardo V. Zimmerman, Guy A. Faria Neto, Hugo C. Castro |
| dc.subject.other.pt_BR.fl_str_mv |
Malária cerebral Estatina Tratamento Neuroinflamação Prevenção Danos cognitivos |
| topic |
Malária cerebral Estatina Tratamento Neuroinflamação Prevenção Danos cognitivos Cerebral Malaria Statin Treatment Neuroinflammation Prevent Cognitive Impairment |
| dc.subject.en.pt_BR.fl_str_mv |
Cerebral Malaria Statin Treatment Neuroinflammation Prevent Cognitive Impairment |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. |
| publishDate |
2012 |
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2012 |
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2017-01-18T14:06:20Z |
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2017-01-18T14:06:20Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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REIS, Patricia Alves et al. Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria. Plos Pathogens, v. 8, n. 12, p. 1- 13, Dec. 2012. |
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https://www.arca.fiocruz.br/handle/icict/16892 |
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1553-7366 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.ppat.1003099 |
| dc.identifier.eissn.none.fl_str_mv |
1553-7374 |
| identifier_str_mv |
REIS, Patricia Alves et al. Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria. Plos Pathogens, v. 8, n. 12, p. 1- 13, Dec. 2012. 1553-7366 10.1371/journal.ppat.1003099 1553-7374 |
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