Influx of T cells into corpus callosum increases axonal injury, but does not change the course of remyelination in toxic demyelination

Abstract

Multiple sclerosis (MS) is a focal inflammatory and demyelinating disease. The inflammatory infiltrates consist of macrophages/microglia, T and B cells. Remyelination (RM) is an endogenous repair process which frequently fails in MS patients. In earlier studies, T cells either promoted or impaired RM. Here, we used the combined cuprizone/MOG‐EAE model to further dissect the functional role of T cells for RM. The combination of MOG immunization with cuprizone feeding targeted T cells to the corpus callosum and increased the extent of axonal injury. Global gene expression analyses demonstrated significant changes in the inflammatory environment; however, additional MOG immunization did not alter the course of RM. Our results suggest that the inflammatory environment in the combined model affects axons and oligodendrocytes differently and that oligodendroglial lineage cells might be less susceptible to T cell mediated injury.

How to Use the Cuprizone Model to Study De- and Remyelination

“…Experiments using the cuprizone model have provided essential insights into the physiology and pathology of remyelination. Among others, this model has been used to demonstrate the importance of vasculature-associated oligodendrocytes [104], investigate the relevance of T-cells for de-and remyelination [105], measure changes of visual evoked potentials during de-and remyelination [106], and understand to what extent de-and remyelination can be assessed using advanced imaging techniques such as ultrahigh-field multiparameter MRI [107].…”