Murine cerebral malaria is associated with a vasospasm-like microcirculatory dysfunction, and survival upon rescue treatment is markedly increased by nimodipine.

I found this to be an important contribution because it is the first study to clearly demonstrate that a major component of the pathogenesis of cerebral malaria in the mouse model is due to vascular dysfunction. Although not an entirely novel concept, it does clearly demonstrate this point.

Cerebral malaria is an important cause of morbidly and mortality, especially among children in sub-Saharan Africa. It is usually caused by infection with Plasmodium falciparum. The mouse model of cerebral malaria employs the ANKA strain of P. berghei. Previously, Kennan et al. reported that in the mouse model there was a reduction in cerebral blood flow {1}. Furthermore, Machado et al. demonstrated that the expression of the vasoactive peptide endothelin-1 was increased in the mouse model {2}. Cabrales et al. now report in an elegant study a decrease in pial arteriolar blood flow and vasoconstriction in infected mice. In addition, leukocyte sequestration contributed to a reduction in pial blood flow. Remarkably, the co-administration of artemether and a calcium channel blocker, nimodipine, caused vasodilation and an increase in pial blood flow. The use of this or related vasodilators may prove to be an important adjuvant in the treatment of cerebral malaria. For further reading, please see {3,4}.

NB: refs {1,2} are from my group.

References: {1} Kennan et al. Parasitol Res 2005, 96:302-7 [PMID:15918069]. {2} Machado et al. Exp Biol Med (Maywood) 2006, 231:1176-81 [PMID:16741072]. {3} Penet et al. J Neurosci 2005, 25:7352-8 [PMID:16093385]. {4} Lacerda-Queiroz et al. Exp Parasitol 2010, Feb 6, Epub ahead of print [PMID:20138873].