Keita M, Bouteille B, Enanga B, Vallat J M, Dumas M
Institut d'épidémiologie neurologique et de neurologie tropicale, Service de Parasitologie, Limoges, France.
Exp Parasitol. 1997 Feb;85(2):183-92. doi: 10.1006/expr.1996.4136.
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 x 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 increasing 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.
在患有脑部病变和神经障碍的动物中寻找人类非洲锥虫病（HAT）的慢性实验模型一直很困难。有人提出使用布氏冈比亚锥虫或布氏罗得西亚锥虫建立脑膜脑炎模型。布氏布氏锥虫感染很少发生脑膜脑炎。已表明用乙酰氨基苯脒（贝尼尔）治疗感染布氏布氏锥虫的小鼠会导致快速脑膜脑炎的发展。在本研究中，我们报告了在感染布氏布氏锥虫AnTat 1.1E的小鼠中建立HAT慢性实验模型的情况。为了使感染有慢性进展，在感染后第21天，给小鼠以20 mg x kg(-1)体重的苏拉明（莫拉尼）剂量进行治疗，该剂量未能清除中枢神经系统（CNS）中的锥虫。在血液中每次寄生虫血症复发后重复这种治疗，使动物在感染后存活超过300天。感染几周后，小鼠出现神经症状。组织学研究表明，随着病变在大脑和小脑实质的血管周围间隙中进展，炎症病变从脑膜炎发展到脑膜脑炎，且病变不断增加。除坏死空间外，未观察到脱髓鞘或神经元改变。在CNS的不同结构中观察到了锥虫。对胶质纤维酸性蛋白（GFAP）的免疫组织化学研究表明，根据感染持续时间，星形细胞增生增加。该模型再现了人类疾病中观察到的神经和组织病理学情况，可用于对这种疾病进行进一步的免疫病理学、神经组织学和治疗研究。
