Carbon monoxide and brain sequestration of Plasmodium berghei ANKA in experimental cerebral malaria

Detalhes bibliográficos
Autor(a) principal: Pena, Ana Catarina Dias
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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spelling 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
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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