Contribution of Oligodendrocytes, Microglia, and Astrocytes to Myelin Debris Uptake in an Explant Model of Inflammatory Demyelination in Rats

: The internalization and degradation of myelin in glia contributes to the resolution of neuroinflammation and influences disease progression. The identification of a three-dimensional experimental model to study myelin processing under neuroinflammation will offer a novel approach for studying treatment strategies favoring inflammation resolution and neuroprotection. Here, by using a model of neuroinflammation in hippocampal explants, we show that myelin debris accumulated immediately after insult and declined at 3 days, a time point at which tentative repair processes were observed. Olig2+ oligodendrocytes upregulated the LRP1 receptor and progressively increased MBP immunoreactivity both at peri-membrane sites and within the cytosol. Oligodendrocyte NG2+ precursors increased in number and immunoreactivity one day after insult, and moderately internalized MBP particles. Three days after insult MBP was intensely coexpressed by microglia and, to a much lesser extent, by astrocytes. The engulfment of both MBP+ debris and whole MBP+ cells contributed to the greatest microglia response. In addition to improving our understanding of the spatial-temporal contribution of glial scarring to myelin uptake under neuroinflammation, our findings suggest that the exposure of hippocampal explants to LPS + IFN-γ-induced neuroinflammation may represent a valuable demyelination model for studying both the extrinsic and intrinsic myelin processing by glia under neuroinflammation.