Trypanosoma brucei brucei: A Long-Term Model of Human African Trypanosomiasis in Mice, Meningo-Encephalitis, Astrocytosis, and Neurological Disorders MAHAMANE KEITA,* , ² , ‡BERNARD BOUTEILLE,* , ²B ERTIN ENANGA,* , ²J EAN-MICHEL VALLAT,‡ AND MICHEL DUMAS* , ‡ *Institut d’e ´pide ´miologie neurologique et de neurologie tropicale, ²Service de Parasitologie, and ‡Servide de Neurologie, Faculte ´ de Me ´decine, 2, rue du Docteur Raymond Marcland, F 87025 Limoges, France KEITA, M., BOUTEILLE, B., ENANGA, B., VALLAT, J. M., AND DUMAS, M. 1997. Trypanosoma brucei brucei: A long-term model of human African trypanosomiasis in mice, meningo-encephalitis, astro- cytosis, and neurological disorders. Experimental Parasitology 85, 183–192. The search for a chronic experimental model for human African trypanosomiasis (HAT) in animals with cerebral lesions and neurological disorders has been difficult. Models with meningo-encephalitis have been proposed using Trypanosoma brucei gambiense or T. b. rhodesiense. Meningo-encephalitis is rare 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, we report the development of a chronic experimental model of HAT in mice 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 dose of suramin (Moranyl) at 20 mg · kg -1 body weight, a dose which failed to eliminate trypanosomes in the central nervous system (CNS). This treatment, repeated after each parasitemic relapse in the blood, allowed animals to survive more than 300 days postinfection. After a few weeks of infection, mice displayed neurological signs. Histological studies showed the appearance of in- creasing inflammatory lesions, from meningitis to meningo-encephalitis, with progression of lesions throughout the perivascular spaces in cerebral and cerebellum parenchyma. No demyelination or neuronal alteration were observed except in the necrotic spaces. Trypanosomes were observed in different structures in CNS. An immunohistochemical study of glial fibrillary acidic protein (GFAP) showed an increasing astrocytosis according to the duration of the infection. This model reproduces neurological and histological pathology observed in the human disease and can be useful for further immunopathological, neurohistological and therapeutic studies on this condition. © 1997 Academic Press INDEX DESCRIPTORS AND ABBREVIATIONS: astrocytosis; meningo-encephalitis; mice; neurological signs; Trypanosoma brucei brucei; BB, blood-brain barrier (BBB); CNS, central nervous system (CNS); EATRO, East African trypanosomiasis research organization (EATRO); GFAP, glial fibril- lary acidic protein (GFAP); HAT, human African trypanosomiasis (HAT); i.p., intraperitoneal (i.p.); LSAB, labeled streptavidin biotin (LSAB); NS, neurological signs (NS); PBS, phosphate buffer saline (PBS); p.i., postinfection (p.i.); PG, prostaglandin (PG). INTRODUCTION Human African trypanosomiasis (HAT), or sleeping sickness, is a fatal disease without treatment caused by Trypanosoma brucei gam- biense or T. b. rhodesiense inoculated by a bite of the tsetse fly (Molyneux et al. 1984). The pathology of HAT usually comprises two stages. The first stage during which try- panosomes are observed in the haemolymphatic system, may include fever, splenomegaly, ad- enopathies, and endocrine disorders. In second stage, trypanosomes are located in the central nervous system (CNS) and a variety of the CNS disturbances have been described, including sensory, motor and psychic disturbances, neu- roendocrine abnormalities, and disturbed circar- dian rhythms (Gallais and Badier 1952; Col- lomb 1957; Greenwood and Whittle 1980; Molyneux et al. 1984; Buguet et al. 1994). His- tological studies in the late stage reveal me- ningo-encephalitis and gliosis (Adams et al. 1986). Immunological and neurohistological mechanisms leading to HAT pathologies are not EXPERIMENTAL PARASITOLOGY 85, 183–192 (1997) ARTICLE NO. PR964136 183 0014-4894/97 $25.00 Copyright © 1997 by Academic Press All rights of reproduction in any form reserved.