Significant oligodendrocyte progenitor and microglial cell death is a feature of remyelination following toxin-induced experimental demyelination

Abstract

The extent to which glial cell turnover features in successful remyelination is unclear. In this study, the rat caudal cerebellar peduncle-ethidium bromide lesion model was used to profile oligodendroglial and microglial/macrophage cell death and proliferation dynamics over the course of repair. Lesioned and control tissue was co-labeled with antibody markers for cell identity, proliferation, and apoptosis (TUNEL assay), then imaged at full thickness using confocal microscopy and quantified using custom CellProfiler pipelines. Early remyelination timepoints were marked by an increased density of total proliferating cells, including oligodendrocyte progenitor cells. Late remyelination timepoints featured increased TUNEL+ oligodendrocyte progenitor cells: however, most TUNEL+ cells within remyelinating lesions were Iba1+ microglia/macrophages. These results indicate that repairing lesions are characterized by a high degree of glial cell death and suggest that monitoring cell death-related byproducts might have clinical value in the setting of remyelination.