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.