Evidence of blood-brain barrier dysfunction in human cerebral malaria

Citation
H. Brown et al., Evidence of blood-brain barrier dysfunction in human cerebral malaria, NEUROP AP N, 25(4), 1999, pp. 331-340
Citations number
33
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
ISSN journal
03051846 → ACNP
Volume
25
Issue
4
Year of publication
1999
Pages
331 - 340
Database
ISI
SICI code
0305-1846(199908)25:4<331:EOBBDI>2.0.ZU;2-W
Abstract
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.