TRYPANOSOMA-BRUCEI-BRUCEI - A LONG-TERM MODEL OF HUMAN AFRICAN TRYPANOSOMIASIS IN MICE, MENINGOENCEPHALITIS, ASTROCYTOSIS, AND NEUROLOGICALDISORDERS

Trypanosoma brucei brucei: A long-term model of human African trypanos omiasis in mice, meningo-encephalitis, astrocytosis, and neurological disorders. Experimental Parasitology 85, 183-192. The search for a chr onic experimental model for human African trypanosomiasis (HAT) in ani mals with cerebral lesions and neurological disorders has been difficu lt. Models with meningo-encephalitis have been proposed using Trypanos oma brucei gambiense or T. b. rhodesiense. Meningo-encephalitis is rar e in infection with T. b. brucei. It has been shown that the treatment of mice infected with T. b. brucei with diminazene aceturate (Berenyl ) led to development of a rapid meningo-encephalitis. In this study, w e report the development of a chronic experimental model of HAT in mic e infected with T. b. brucei AnTat 1.1E. To obtain a chronic evolution of the infection, on Day 21 postinfection, mice were treated with a d ose of suramin (Moranyl) at 20 mg . kg(-1) body weight, a dose which f ailed to eliminate trypanosomes in the central nervous system (CNS). T his treatment, repeated after each parasitemic relapse in the blood, a llowed animals to survive more than 300 days postinfection. After a fe w weeks of infection, mice displayed neurological signs. Histological studies showed the appearance of increasing inflammatory lesions, from meningitis to meningo-encephalitis, with progression of lesions throu ghout the perivascular spaces in cerebral and cerebellum parenchyma. N o demyelination or neuronal alteration were observed except in the nec rotic spaces. Trypanosomes were observed in different structures in CN S. An immunohistochemical study of glial fibrillary acidic protein (GF AP) showed an increasing astrocytosis according to the duration of the infection. This model reproduces neurological and histological pathol ogy observed in the human disease and can be useful for further immuno pathological, neurohistological and therapeutic studies on this condit ion. (C) 1997 Academic Press.