Nucleoside analogues effect on glial response in experimental autoimmune encephalomyelitis

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an animal model of human disease multiple sclerosis (MS). Clinical signs of EAE are result of an autoaggressive T-cell response against myelin. We have previously shown that combined treatment with nucleoside analogues (ribavirin — R +tiazofurin — T), inosine monophosphate dehydrogenase inhibitors, ameliorates clinical signs and histological lesions of EAE in susceptible rats, when they are given preventatively. The aim of this study was to investigate the effect of combined treatment with R+T, given with the appearance of first EAE clinical sign, on microglia and astrocytes response. These cells of the target tissue also participate in an autoimmune process. The disease was induced in Dark Agouti rats with rat spinal cord homogenate and had acute monophasic course. Ribavirin and tiazofurin were given at a dosage of 30 mg/kg/day and 10 mg/kg every other day, for 15 days, respectively. Control group was immunized and treated with saline. Amelioration of clinical signs and faster recovery was shown in group treated with combination of R and T in comparison to control group. Immunohistochemical analysis of the spinal cord tissue isolated after 15 days of combined therapy revealed decrease in vimentin positive cells and microglia compared to control group. Additionally, morphology of GFAP positive (glial fibrillary acid protein) cells and microglia indicated to reactive type of these cells in control group. Results of this study revealed that R and T modulate glial response and have EAE protective effects when they are given from the onset of disease.