Blood-brain barrier damage in experimental African trypanosomiasis

Abstract

African sleeping sickness is characterized by progressive central nervous system (CNS) involvement, leading to the so-called secondary or late stage in which there are widespread inflammatory changes with lymphoplasmocytic infiltration. A study was made of blood-brain barrier (BBB) integrity in the late stages of a rodent model by assessing the uptake of the fluorescent fluid-phase marker sulphorhodamine B into the brain tissue. Brain oedema was estimated from brain weight, density and electrolyte concentrations. Trypanosome distribution was studied by light and electron microscopy. At 35 days post-infection (p.i.) fluorescent dye penetration occurred in several brain regions, including thalamus and hypothalamus. At 40 days p.i., BBB damage was extensive, with dye penetration throughout both the grey and the white matter of the cortex. Infected rats had significantly higher brain water content than uninfected controls and altered sodium and potassium concentrations characteristic of vasogenic oedema. The morphological studies showed early accumulation of parasites within, and associated damage to the choroid plexus, and, in the late stages, the presence of small numbers of trypansomes scattered in the nerve tissue of the brain and spinal cord, similar to previous descriptions. The findings show that chronic trypanosomiasis in the rat model is accompanied by BBB damage and vasogenic oedema.