Memorias do Instituto Oswaldo Cruz (Aug 2014)

Vascular dysfunction as a target for adjuvant therapy in cerebral malaria

  • Leonardo José de Moura Carvalho,
  • Aline da Silva Moreira,
  • Cláudio Tadeu Daniel-Ribeiro,
  • Yuri Chaves Martins

DOI
https://doi.org/10.1590/0074-0276140061
Journal volume & issue
Vol. 109, no. 5
pp. 577 – 588

Abstract

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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.

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