Specific Components Associated With the Endothelial Glycocalyx Are Lost From Brain Capillaries in Cerebral Malaria
- 12 May 2022
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 226 (8), 1470-1479
- https://doi.org/10.1093/infdis/jiac200
Abstract
Cerebral malaria (CM) is a rare, but severe and frequently fatal outcome of infections with Plasmodium falciparum. Pathogenetic mechanisms include endothelial activation and sequestration of parasitized erythrocytes in the cerebral microvessels. Increased concentrations of glycosaminoglycans in urine and plasma of malaria patients have been described, suggesting involvement of endothelial glycocalyx. We used lectin histochemistry on postmortem samples to compare the distribution of multiple sugar epitopes on cerebral capillaries in children who died from CM and from non-malarial comas. N-acetyl glucosamine residues detected by tomato lectin are generally reduced in children with CM compared to controls. We used the vascular expression of intercellular adhesion molecule-1 and mannose residues on brain capillaries of CM as evidence of local vascular inflammation, and both were expressed more highly in CM patients than controls. Sialic acid residues were found to be significantly reduced in patients with CM. By contrast, the levels of other sugar epitopes regularly detected on the cerebral vasculature were unchanged, and this suggests specific remodeling of cerebral microvessels in CM patients. Our findings support and expand upon earlier reports of disruptions of the endothelial glycocalyx in children with severe malaria.Keywords
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