title: Vascular dysfunction as a target for adjuvant therapy in cerebral malaria.
abstract: Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum malaria that continues to be a major global health problem. Brain vascular dysfunction is a main factor underlying the pathogenesis of CM and can be a target for the development of adjuvant therapies for the disease. Vascular occlusion by parasitised red blood cells and vasoconstriction/vascular dysfunction results in impaired cerebral blood flow, ischaemia, hypoxia, acidosis and death. In this review, we discuss the mechanisms of vascular dysfunction in CM and the roles of low nitric oxide bioavailability, high levels of endothelin-1 and dysfunction of the angiopoietin-Tie2 axis. We also discuss the usefulness and relevance of the murine experimental model of CM by Plasmodium berghei ANKA to identify mechanisms of disease and to screen potential therapeutic interventions.
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Leonardo José de Moura
authors.initials: LJ
authors.lastname: Carvalho
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Aline da Silva
authors.initials: Ada S
authors.lastname: Moreira
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Cláudio Tadeu
authors.initials: CT
authors.lastname: Daniel-Ribeiro
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Yuri Chaves
authors.initials: YC
authors.lastname: Martins
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000469:parasitology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D016232:Endothelins / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D016779:Malaria, Cerebral / Q000469:parasitology / Q000503:physiopathology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; D016232:Endothelins; D009569:Nitric Oxide