Blood-brain barrier function in cerebral malaria in Malawian children

• Published in: The American journal of tropical medicine and hygiene Vol. 64; no. 3; pp. 207 - 213
• Main Authors: Brown, H, Rogerson, S, Taylor, T, Tembo, M, Mwenechanya, J, Molyneux, M, Turner, G
• Format: Journal Article
• Language: English
• Published: Lawrence, KS ASTMH 01.03.2001; Allen Press
• Subjects: Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Biological and medical sciences; Blood Proteins - metabolism; Blood-Brain Barrier - physiology; Case-Control Studies; cerebral malaria; Child, Preschool; Epithelial Attachment - metabolism; Female; Human protozoal diseases; Humans; Immunohistochemistry; Infant; Infectious diseases; Malaria; Malaria, Cerebral - epidemiology; Malaria, Cerebral - physiopathology; Malawi - epidemiology; Male; Medical sciences; Parasitic diseases; Plasmodium falciparum; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Protozoal diseases; Tropical medicine; Malawi; Africa; Human; Infection; Pathology; Protozoal disease; Cerebral cortex; Malaria; Pathophysiology; Pernicious attack; Parasitosis; Blood brain barrier; Child; Brain (vertebrata)
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.2001.64.207

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.