Patients infected with the malaria parasite Plasmodium falciparum may devel
op a diffuse reversible encephalopathy, termed cerebral malaria. It is uncl
ear how the intraerythrocytic parasite, which sequesters in the cerebral mi
crovasculature but does not enter the brain parenchyma, induces this neurol
ogical syndrome.
Adhesion of parasitized red blood cells in the brain microvasculature is me
diated by specific receptors on the host endothelium, including intercellul
ar adhesion molecule (ICAM)-1, CD36 and CD31. Leucocyte binding to cerebral
endothelial cells in culture induces intracellular signalling via ICAM-1.
The hypothesis that parasitized red blood cells binding to receptors on cer
ebral endothelial cells causes changes in the integrity of the blood-brain
barrier was tested.
Immunohistochemistry was used to examine the blood-brain barrier in human c
erebral malaria, with antibodies to macrophage and endothelial activation m
arkers, intercellular junction proteins, and plasma proteins. The distribut
ion of the cell junction proteins occludin, vinculin and ZO-1 were altered
in cerebral malaria cases compared to controls. While fibrinogen was the on
ly plasma protein detected in the perivascular space, there was widespread
perivascular macrophage activation, suggesting that these cells had been ex
posed to plasma proteins.
It was concluded that functional changes to the blood-brain barrier occur i
n cerebral malaria, possibly as a result of the binding of parasitized red
blood cells to cerebral endothelial cells. These changes require further ex
amination in vitro.