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Blood-brain barrier function in cerebral malaria in Malawian children
H Brown1, S Rogerson, T Taylor
1Nuffield Department of Clinical Laboratory Sciences, The John Radcliffe Hospital, Oxford, United Kingdom.
Insights
Cerebral malaria (CM) involves infected red blood cells sticking to brain vessels. This study found subtle blood-brain barrier (BBB) changes in children with CM, suggesting localized breakdown during Plasmodium falciparum infection.
Area of Science:
- Neuroscience
- Infectious Diseases
- Pathology
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection.
- Parasitized erythrocyte sequestration in cerebral endothelium is central to CM pathogenesis.
- Clinical manifestations differ between African children (neurological symptoms) and adults (organ failure).
Purpose of the Study:
- To investigate blood-brain barrier (BBB) structural and functional changes in Malawian children with CM.
- To correlate BBB alterations with observed neurological signs and symptoms.
Main Methods:
- Immunohistochemistry on autopsy brain tissues from eight CM cases.
- Analysis of albumin distribution between plasma and cerebrospinal fluid in 72 CM cases.
Main Results:
- Endothelial cell and macrophage activation observed in vessels with sequestered parasitized erythrocytes.
- Disruption of endothelial intercellular junctions noted, without gross plasma protein leakage.
- Subtle, measurable changes in albumin partition indicated impaired BBB function.
Conclusions:
- Blood-brain barrier (BBB) breakdown is associated with parasite sequestration in pediatric CM.
- These BBB changes are compatible with the neurological symptoms seen in CM patients.
- Findings highlight localized BBB dysfunction in the pathogenesis of cerebral malaria.
Abstract:
Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection. Binding of parasitized erythrocytes to cerebral endothelium plays a key role in disease pathogenesis. Central nervous system signs and symptoms (coma, seizures, raised intracranial pressure) predominate in African children, whereas in adults, multiorgan system failure is more common. In this study we investigated whether changes in blood-brain barrier (BBB) structure and function are compatible with the signs and symptoms observed in Malawian children with CM. Immunohistochemistry on autopsy brain tissues from eight cases of CM showed activation of endothelial cells and macrophages, and disruption of endothelial intercellular junctions in vessels containing sequestered parasitized erythrocytes, but no gross leakage of plasma proteins. Examination of the partition of albumin between circulating plasma and the cerebrospinal fluid from 72 cases of CM showed subtle but measurable changes compatible with impaired BBB function in malaria. These findings suggest that BBB breakdown occurs in areas of parasite sequestration in CM in African children.