Effect of Hematopoietic Stem Cell Transplantation and Post-Transplantation Cyclophosphamide on the Microglia Phenotype in Rats with Experimental Allergic Encephalomyelitis

Abstract

Microglia are the resident immune cells of the central nervous system, playing a role in the inflammatory process development and resolution, presenting two main phenotypes, pro-inflammatory M1, and anti-inflammatory M2. Therapies affecting the microglia phenotype may be beneficial in treating inflammatory neurodegenerative diseases. In our experiments, we used the animal multiple sclerosis model, experimental allergic encephalomyelitis (EAE). Rats were treated during the pre- or symptomatic phase of the disease with cyclophosphamide, followed by hematopoietic stem cell transplantation, and with/without post-transplantation cyclophosphamide. Our study aimed to analyze the microglia phenotype in animals subjected to this treatment. The number of M1 cells in the spinal cord, and inducible nitric oxide synthase (iNOS) levels in the brain were similar in all experimental groups. The differences were observed in M2 cells number and arginase 1 (Arg1) levels, which were decreased in EAE animals, and increased after treatment in the symptomatic phase of EAE, and in the pre-symptomatic phase, but only with post-transplantation cyclophosphamide. Analysis of gene expression in the brain showed decreased iNOS expression in EAE animals treated in the symptomatic phase of EAE and no differences in Arg1 expression. Results indicate that treatment applied to experimental animals influences the microglia phenotype, promoting differentiation towards M2 cells.