Identification of the adult resting progenitor cell by autoradiographic tracking of oligodendrocyte precursors in experimental CNS demyelination.

The new population of oligodendrocytes remyelinating an experimental demyelinating optic nerve lesion has been tracked backwards in time. Using autoradiography combined with electron microscopy and immunocytochemistry, serial sections of optic nerves from young adult cats were studied from 42 h (2 days) post-injection to 93 h (4 days) post-injection. The remyelinating oligodendrocyte lineage was found to commence with the single division of a resting progenitor cell residing in a central fascicular location outside the demyelinative lesion. The division of the founding progenitor cell occurs at 2 days post-lesion and results in two motile daughter cells. These cells, previously described by us as precursor cells, migrate to the lesion, closely appose demyelinated axons, produce axon wrapping processes and differentiate to become remyelinating oligodendrocytes. This study confirms that remyelinating oligodendrocytes originate from resting progenitor cells outside the lesion and not from mature oligodendrocytes, and implies that repeated demyelinative injury could exhaust the reparative capacity of such a region.