Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria
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Data de Publicação: | 2009 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/1493 |
Resumo: | Tese de mestrado, Biologia (Biologia Celular e Biotecnologia), 2009, Universidade de Lisboa, Faculdade de Ciências |
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Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malariaBiologia celularMalária cerebralCélulas TTeses de mestradoTese de mestrado, Biologia (Biologia Celular e Biotecnologia), 2009, Universidade de Lisboa, Faculdade de CiênciasResumo alargado em português disponível no documentoMalaria is a major infectious disease worldwide, causing ~1 million deaths each year due to severe complications, one of the most lethal being cerebral malaria (CM). Thereby, understanding CM pathogenesis is of vital importance for developing effective therapies against it. The experimental cerebral malaria (ECM) model of C57BL/6 mice infected with P. berghei ANKA (PbA) shares many similarities with human CM. However, whereas in humans a critical event is sequestration of Plasmodium-infected red blood cells (iRBCs) in the brain microvasculature, in rodents is mostly leukocyte sequestration that occurs. Thereby, the pathologic significance of iRBCs brain sequestration during ECM is controversial and remains to be clarified. Recently, it was shown that heme-oxygenase-1 (HO-1) plays a crucial role in protection against ECM, which appears to be mediated by carbon monoxide (CO) production, an end-product of its enzymatic activity. In fact, administration of CO by inhalation rescues all C57BL/6 PbA-infected mice from developing ECM. The present study shows that CO protection comprises the reduction of iRBC brain sequestration in infected mice, supporting the importance of this process in ECM pathogenesis and the relevance of C57BL/5 PbA-infected mouse model to study CM. Moreover, our results indicate that CO has a therapeutic potential as a molecule with anti-inflammatory and anti-chemotaxis effects. We also demonstrate that CORM-2, a CO-relasing molecule (CORM-2), mimics CO protection against ECM, suppressing neuroinflammation and parasite sequestration in the brain. Importantly, CORM-2 does not induce formation of carboxyhemoblogin, circumventing CO inhalation toxicity. Moreover, CORM-2 inhibits platelet aggregation and loss of RBC deformability, which likely contributes to prevent disease development. Additionally, CORM-2 also leads to an arrest in parasite load, which origin and relevance is not clear. Altogether, these results indicate that CO-RMs seem to represent a novel class of drugs with therapeutic potential to protect the host from cerebral malaria.Pamplona, AnaZilhão, Rita Maria Pulido GarciaRepositório da Universidade de LisboaPena, Ana Catarina Dias2010-07-27T08:58:38Z20092009-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdftext/xmlhttp://hdl.handle.net/10451/1493enghttp://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000574405info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:41:14Zoai:repositorio.ul.pt:10451/1493Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:28:07.513952Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria |
title |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria |
spellingShingle |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria Pena, Ana Catarina Dias Biologia celular Malária cerebral Células T Teses de mestrado |
title_short |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria |
title_full |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria |
title_fullStr |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria |
title_full_unstemmed |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria |
title_sort |
Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria |
author |
Pena, Ana Catarina Dias |
author_facet |
Pena, Ana Catarina Dias |
author_role |
author |
dc.contributor.none.fl_str_mv |
Pamplona, Ana Zilhão, Rita Maria Pulido Garcia Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Pena, Ana Catarina Dias |
dc.subject.por.fl_str_mv |
Biologia celular Malária cerebral Células T Teses de mestrado |
topic |
Biologia celular Malária cerebral Células T Teses de mestrado |
description |
Tese de mestrado, Biologia (Biologia Celular e Biotecnologia), 2009, Universidade de Lisboa, Faculdade de Ciências |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009 2009-01-01T00:00:00Z 2010-07-27T08:58:38Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/1493 |
url |
http://hdl.handle.net/10451/1493 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
http://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000574405 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf text/xml |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134164141735936 |