A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver

Detalhes bibliográficos
Autor(a) principal: Martins, Yuri Chaves
Data de Publicação: 2013
Outros Autores: Daniel-Ribeiro, Cláudio Tadeu
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/12029
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Centro de Pesquisa Diagnóstico e Treinamento em Malária. Rio de Janeiro, RJ, Brasil / Albert Einstein College of Medicine. Department of Pathology. The Bronx, NY, USA.
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spelling Martins, Yuri ChavesDaniel-Ribeiro, Cláudio Tadeu2015-10-22T12:13:53Z2015-10-22T12:13:53Z2013MARTINS, Yuri Chaves; DANIEL-RIBEIRO, Cláudio Tadeu. A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver. Medical Hypotheses, v.81, n.5, p.777–783, nov. 2013.0306-9877https://www.arca.fiocruz.br/handle/icict/1202910.1016/j.mehy.2013.08.005engElsevierMalária CerebralPlasmodium falciparumCerebral MalariaPlasmodium falciparumA new hypothesis on the manifestation of cerebral malaria: The secret is in the liverinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Centro de Pesquisa Diagnóstico e Treinamento em Malária. Rio de Janeiro, RJ, Brasil / Albert Einstein College of Medicine. Department of Pathology. The Bronx, NY, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Centro de Pesquisa Diagnóstico e Treinamento em Malária. Rio de Janeiro, RJ, Brasil.Despite the abundance of information on cerebral malaria (CM), the pathogenesis of this disease is not completely understood. At present, two nonexclusive dominant hypotheses exist to explain how the neurological syndrome manifests: the sequestration (or mechanical) hypothesis and the inflammatory hypothesis. The sequestration hypothesis states that sequestration of Plasmodium falciparum-parasitized red blood cells (pRBCs) to brain capillary endothelia causes obstruction of capillary blood flow followed by brain tissue anoxia and coma. The inflammatory hypothesis postulates that P. falciparum infection releases toxic molecules in the circulation, inducing an imbalanced systemic inflammatory response that leads to coagulopathy, brain endothelial cell dysfunction, accumulation of leukocytes in the brain microcirculation, blood brain barrier (BBB) leakage, cerebral vasoconstriction, edema, and coma. However, both hypotheses, even when considered together, are not sufficient to fully explain the pathogenesis of CM. Here, we propose that the development of acute liver failure (ALF) together with BBB breakdown are the necessary and sufficient conditions for the genesis of CM. ALF is characterized by coagulopathy and hepatic encephalopathy (HE) in a patient without pre-existing liver disease. Signs of hepatic dysfunction have been shown to occur in 2.5–40% of CM patients. In addition, recent studies with murine models demonstrated that mice presenting experimental cerebral malaria (ECM) had hepatic damage and brain metabolic changes characteristic of HE. However, the occurrence of CM in patients with mild or without apparent hepatocellular liver damage and the presence of liver damage in non-CM murine models indicate that the development of ALF during malaria infection is not the single factor responsible for neuropathology. To solve this problem, we also propose that BBB breakdown contributes to the pathogenesis of CM and synergizes with hepatic failure to cause neurological signs and symptoms. BBB dysfunction would thus occur in CM by a mechanism similar to the one occurring in sepsis and is in agreement with the inflammatory hypothesis. Nevertheless, differently from in the inflammatory hypothesis, BBB leakage would facilitate the penetration of ammonia and other toxins into the brain parenchyma, but would not be sufficient to cause CM when occurring alone. We believe our hypothesis better explains the pathogenesis of CM, does not have problems to deal with the exception data not explained by the previous hypotheses, and reveals new targets for adjunctive therapy.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://www.arca.fiocruz.br/bitstream/icict/12029/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALyuri_martins_ribeiro_IOC_2013.pdfyuri_martins_ribeiro_IOC_2013.pdfapplication/pdf342330https://www.arca.fiocruz.br/bitstream/icict/12029/2/yuri_martins_ribeiro_IOC_2013.pdf2bfd20cbf56abdfbb32216aeb460ac7aMD52TEXTyuri_martins_ribeiro_IOC_2013.pdf.txtyuri_martins_ribeiro_IOC_2013.pdf.txtExtracted texttext/plain50219https://www.arca.fiocruz.br/bitstream/icict/12029/3/yuri_martins_ribeiro_IOC_2013.pdf.txt85a50c055a3ec05a4555ae88c649565eMD53icict/120292023-09-05 10:36:26.835oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-05T13:36:26Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
title A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
spellingShingle A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
Martins, Yuri Chaves
Malária Cerebral
Plasmodium falciparum
Cerebral Malaria
Plasmodium falciparum
title_short A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
title_full A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
title_fullStr A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
title_full_unstemmed A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
title_sort A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver
author Martins, Yuri Chaves
author_facet Martins, Yuri Chaves
Daniel-Ribeiro, Cláudio Tadeu
author_role author
author2 Daniel-Ribeiro, Cláudio Tadeu
author2_role author
dc.contributor.author.fl_str_mv Martins, Yuri Chaves
Daniel-Ribeiro, Cláudio Tadeu
dc.subject.other.pt_BR.fl_str_mv Malária Cerebral
Plasmodium falciparum
topic Malária Cerebral
Plasmodium falciparum
Cerebral Malaria
Plasmodium falciparum
dc.subject.en.pt_BR.fl_str_mv Cerebral Malaria
Plasmodium falciparum
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Centro de Pesquisa Diagnóstico e Treinamento em Malária. Rio de Janeiro, RJ, Brasil / Albert Einstein College of Medicine. Department of Pathology. The Bronx, NY, USA.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2015-10-22T12:13:53Z
dc.date.available.fl_str_mv 2015-10-22T12:13:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv MARTINS, Yuri Chaves; DANIEL-RIBEIRO, Cláudio Tadeu. A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver. Medical Hypotheses, v.81, n.5, p.777–783, nov. 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/12029
dc.identifier.issn.none.fl_str_mv 0306-9877
dc.identifier.doi.none.fl_str_mv 10.1016/j.mehy.2013.08.005
identifier_str_mv MARTINS, Yuri Chaves; DANIEL-RIBEIRO, Cláudio Tadeu. A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver. Medical Hypotheses, v.81, n.5, p.777–783, nov. 2013.
0306-9877
10.1016/j.mehy.2013.08.005
url https://www.arca.fiocruz.br/handle/icict/12029
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dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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