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Published on: June 8, 2017
Specific Components Associated With the Endothelial Glycocalyx Are Lost From Brain Capillaries in Cerebral Malaria
Casper Hempel1, Dan Milner2,3, Karl Seydel4,5
1Department of Health Technology, Technical University of Denmark, Kgs Lyngby, Denmark.
Background:
Cerebral malaria (CM) is a rare, but severe and frequently fatal outcome of infection 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.
Methods:
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 nonmalarial comas.
Results:
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.
Conclusions:
Our findings support and expand upon earlier reports of disruptions of the endothelial glycocalyx in children with severe malaria.
Insights
Cerebral malaria (CM) in children involves damage to the brain
Area of Science:
- Neurology
- Pathology
- Immunology
Background:
- Cerebral malaria (CM) is a severe Plasmodium falciparum complication.
- Endothelial activation and parasite sequestration in cerebral microvessels contribute to CM pathogenesis.
- Elevated glycosaminoglycans suggest endothelial glycocalyx involvement in malaria.
Purpose of the Study:
- To investigate alterations in the cerebral microvasculature's sugar epitopes in pediatric CM.
- To compare the distribution of sugar epitopes on cerebral capillaries in CM and non-CM fatal cases.
Main Methods:
- Lectin histochemistry was performed on postmortem brain samples.
- Distribution of sugar epitopes on cerebral capillaries was analyzed.
- Comparison was made between children deceased from CM and non-malarial causes.
Main Results:
- Reduced N-acetyl glucosamine residues were observed in CM patients.
- Increased expression of intercellular adhesion molecule 1 and mannose residues indicated vascular inflammation in CM.
- Significantly reduced sialic acid residues were found in CM patients, suggesting specific microvessel remodeling.
Conclusions:
- Findings support and extend previous reports of endothelial glycocalyx disruption in severe pediatric malaria.
- Specific remodeling of cerebral microvessels occurs in pediatric CM.
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