Astrocytes--friends or foes in multiple sclerosis?

In multiple sclerosis (MS), the presence of demyelinating plaques has concentrated researchers' minds on the role of the oligodendrocyte in its pathophysiology. Recently, with the rediscovery of early and widespread loss of axons in the disease, new emphasis has been put on the role of axons and axon-oligodendrocyte interactions in MS. Despite the fact that, in 1904, Müller claimed that MS was a disease of astrocytes, more recently, astrocytes have taken a back seat, except as the cells that form the final glial scar after all hope of demyelination is over. However, perhaps it is time for the return of the astrocyte to popularity in the pathogenesis of MS, with recent reports on the dual role of astrocytes in aiding degeneration and demyelination, by promoting inflammation, damage of oligodendrocytes and axons, and glial scarring, but also in creating a permissive environment for remyelination by their action on oligodendrocyte precursor migration, oligodendrocyte proliferation, and differentiation. We review these findings to try to provide a cogent view of astrocytes in the pathology of MS.