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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 109, No. 5, 2014, pp. 577-588
Bioline Code: oc14091
Full paper language: English
Document type: Review Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 109, No. 5, 2014, pp. 577-588

 en Vascular dysfunction as a target for adjuvant therapy in cerebral malaria
Carvalho, Leonardo José de Moura; da Silva Moreira, Aline; Daniel-Ribeiro, Cláudio Tadeu & Martins, Yuri Chaves

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.

Keywords
cerebral malaria; vascular dysfunction; nitric oxide

 
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