Trypanosoma brucei brucei crosses the blood-brain barrier while tight junction proteins are preserved in a rat chronic disease model

• Published in: Neuropathology and applied neurobiology Vol. 27; no. 1; pp. 77 - 85
• Main Authors: Mulenga, C., Mhlanga, J. D. M., Kristensson, K., Robertson, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-02-2001; Blackwell Science
• Subjects: Animals; Biological and medical sciences; blood-brain barrier; Blood-Brain Barrier - physiology; Brain - blood supply; Brain - metabolism; Brain - parasitology; Brain - pathology; Chronic Disease; Disease Models, Animal; Disease Progression; endothelial cells; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Fibrinogen - metabolism; Glucose Transporter Type 1; Host-Parasite Interactions; Human protozoal diseases; Infectious diseases; inflammation; Intercellular Adhesion Molecule-1 - metabolism; Male; Medical sciences; Medicin och hälsovetenskap; Membrane Proteins - metabolism; Microcirculation - metabolism; Microcirculation - parasitology; Monosaccharide Transport Proteins - metabolism; nervous system; Occludin; Parasitic diseases; Phosphoproteins - metabolism; Protozoal diseases; Rats; Tight Junctions - metabolism; Tight Junctions - ultrastructure; Trypanosoma brucei; Trypanosoma brucei brucei - pathogenicity; Trypanosomiasis; Trypanosomiasis, African - metabolism; Trypanosomiasis, African - parasitology; Trypanosomiasis, African - pathology; Vascular Cell Adhesion Molecule-1 - metabolism; Zonula Occludens-1 Protein; Kinetoplastida; Protozoa; Animal model; Protozoal disease; Pathophysiology; Rat; Rodentia; Parasitosis; African sickness; Blood brain barrier; Infection; Vertebrata; Chronic; Mammalia; Animal; Trypanosoma brucei; Trypanosomiasis
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1046/j.0305-1846.2001.00306.x

African trypanosomiasis, sleeping sickness in humans, is caused by the systemic infection of the host by the extracellular parasite, the African trypanosome. The pathogenetic mechanisms of the severe symptoms of central nervous system involvement are still not well understood. The present study examined the routes of haematogenous spread of Trypanosoma brucei brucei (Tbb) to the brain, in particular on the question whether parasites can cross the blood–brain barrier, as well as their effect on tight junction proteins. Rats were infected with Tbb and at various times post‐infection, the location of the parasite in the central nervous system was examined in relation to the brain vascular endothelium, visualized with an anti‐glucose transporter‐1 antibody. The tight junction‐specific proteins occludin and zonula occludens 1, and the possible activation of the endothelial cell adhesion molecules ICAM‐1 and VCAM‐1 were also studied. At 12 and 22 days post‐infection, the large majority of parasites were confined within blood vessels. At this stage, however, some parasites were also clearly observed in the brain parenchyma. This was accompanied by an upregulation of ICAM‐1/VCAM‐1. At later stages, 42, 45 and 55 days post‐infection, parasites could still be detected within or in association with blood vessels. In addition, the parasite was now frequently found in the brain parenchyma and the extravasation of parasites was more prominent in the white matter than the cerebral cortex. A marked penetration of parasites was seen in the septal nuclei. In spite of this, occludin and zonula occludens 1 staining of the vessels was preserved. The results indicate that the Tbb parasite is able to cross the blood–brain barrier in vivo, without a generalized loss of tight junction proteins.