Multimodal analysis in acute and chronic experimental autoimmune encephalomyelitis

Abstract

Different experimental autoimmune encephalomyelitis models (EAE) have been developed. However, due to the different experimental conditions applied, observations simultaneously considering different pathological targets are still scarce. Using EAE induced in Dark Agouti rats with syngenic whole spinal cord homogenate suspended in incomplete Freund's adjuvant, we here analyze neurosteroidogenic machinery, cytokine levels, microglial cells, infiltration of inflammatory cells, myelin proteins and Na(+), K(+)-ATPase pump activity in the spinal cord. Data obtained in the acute phase of the disease confirmed that neurological signs were accompanied by the presence of perivascular infiltrating T cells (CD3(+) cells) and activated monocytic/microglial cells (ED1(+) and MHC-II(+)) in the spinal cord. In particular, the number of MHC-II(+) cells was significantly increased in association with increased expression of pro- (i.e., TNF-α, IL-1β) and anti-inflammatory (i.e., TGF-β) cytokines as well as with decreased expression of proteolipid protein and myelin basic protein. During the chronic phase of the disease, the number of MHC-II(+) cells was still increased, although less than in the acute phase. Changes in the number of MHC-II(+) cells were associated with decreased Na(+),K(+)-ATPase enzymatic activity. A general decrease in the levels of neuroactive steroids, with the exception of an increase in tetrahydroprogesterone and 17β-estradiol, was detected in the acute phase. These changes were maintained or reverted in the chronic phase of EAE. In conclusion, we report that modifications in the neuroimmune response in the acute and chronic phases of EAE are associated with specific changes in myelin proteins, Na(+),K(+)-ATPase pump and in the levels of neuroactive steroids.