Early recruitment of oligodendrocyte precursors in CNS demyelination.

The source of the new population of oligodendrocytes which successfully remyelinates experimentally induced demyelination of the cat optic nerve was studied with a combination of techniques. These included correlative light microscopy, immunocytochemistry, electron microscopy and autoradiography in transverse and longitudinal sections. Extending the analysis from the newly generated oligodendrocyte back to the very early demyelinative phase of the lesion enabled the identification of a glial precursor cell (GPC) outside the lesion which appeared to be readily recruitable and motile. This cell is likely to be the product of the division of a putative resting progenitor cell residing in a central fascicular location of the normal optic nerve surrounding the lesion. On arriving at the fringe of the lesion, GPCs are transformed into vimentin-positive small glial cells (SGCs) possibly by signals from demyelinated axons to which the SGCs become closely apposed. Small glial cells, which together with GPCs share several features in common with O-2A perinatal progenitors of the rodent optic nerve, then differentiate into oligodendrocytes. Together these findings suggest that the events leading to remyelination of adult mammalian optic nerve commence soon after the demyelinating injury and might recapitulate the principal events of developmental myelinogenesis.