Microglia activation in a model of sleep disorder: an immunohistochemical study in the rat brain during Trypanosoma brucei infection

Microglial cells play a key role in the events triggered by infection, inju ry or degeneration in the central nervous system not only as scavenger cell s but also as immune effector elements. We analyzed the features and distri bution of cells of the microglia/macrophage lineage with OX-42 and ED-1 imm unohistochemistry in the brain of experimental rats infected with the extra cellular parasite Trypanosoma brucei. Such experimental infection provides a rat model of sleeping sickness or African trypanosomiasis, and is hallmar ked in its advanced stages by severe alterations of the animals' sleep stru cture. In infected rats a remarkable activation of microglia, revealed by O X-42 immunoreactivity, became evident in the 3rd week post-infection in per iventricular and subpial brain regions, with a prevalence in the hypothalam us. These features were concomitant with the onset of sleep anomalies, moni tored with electroencephalographic recordings. Microglia activation increas ed in the following weeks, paralleling the progressive alterations of sleep parameters, and was most marked in the terminal stages of the infection, c orresponding to the 6th-7th weeks. In addition, ED-1-immunoreactive macroph ages and ramified microglia, confined to hypothalamic periventricular and b asal regions, were evident after 4 weeks of disease. Degeneration of neuron al perikarya was not detected histologically in the infected brains at any time point. These data provide evidence for a reaction of microglia and mac rophages in the brain of trypanosome-infected rats, and point out a selecti ve distribution of these activated cells. The findings are discussed in rel ation to the animals' sleep disorder during trypanosome infection. (C) 1999 Elsevier Science B.V. All rights reserved.