Local recruitment of remyelinating cells in the repair of demyelination in the central nervous system.

The distance over which remyelinating cells within surrounding intact tissue are stimulated to respond to a demyelinating lesion and migrate toward it is unknown. To address this issue we have conducted a series of experiments in which the generation of remyelinating cells in tissue surrounding a spontaneously repairing area of demyelination induced in the adult rat spinal cord is suppressed by exposure to X-irradiation. By regulating the area of X-irradiation relative to the length of the demyelinating lesion within dorsal white matter we have shown that remyelinating cells are not recruited over distances greater than 2 mm into areas of demyelination, implying that most of the remyelinating cells are locally generated. This result indicates that there is only a narrow rim of normal tissue surrounding an area of demyelination from which remyelinating cells can be recruited. The depletion of cells within this rim may account for the poor remyelination associated with large areas of demyelination and following repeated episodes of demyelination. We have also shown that, in contrast to Schwann cells, oligodendrocyte lineage cells recruited into lesions have a limited ability to rapidly repopulate large areas of demyelination. Attempts to enhance remyelination in situations where it fails should therefore focus on increasing the size of the surrounding area from which remyelinating cells can be recruited by augmenting the level of recruitment signal, and preventing premature differentiation of oligodendrocytes so as to maximize their migratory and proliferative potential.