Role of adult oligodendrocytes in remyelination after neural injury.

Traumatic neural injury is often accompanied by demyelination. The factors that determine the ability of the CNS to remyelinate are examined as well as the origin of the cells responsible for the remyelination. Evidence is presented that suggests that both a precursor-type oligodendrocyte as well as an oligodendrocyte that previously formed a myelin sheath are able to remyelinate in the CNS. A key determinate of the success of remyelination is the ability for either cell type to proliferate before remyelination. We have developed a method to isolate the oligodendrocyte from the mature CNS and studied the mitotic potential of these adult oligodendrocytes in vitro. In contrast to neonatal oligodendrocytes, the adult oligodendrocytes respond weakly to soluble and particulate mitogens. However, when cocultured with neurites, the adult oligodendrocytes demonstrate a more vigorous mitotic response, which may be related to the ability of the neurite to upregulate receptors which transduce the mitotic signal. Since we have identified fibroblast growth factor as a mitogen associated with the axonal plasma membrane that stimulates neonatal oligodendrocytes to divide, we have examined the redistribution of membrane-associated fibroblast growth factor in an in vitro model of neuronal injury. After neuritic injury, fibroblast growth factor containing membrane vesicles were redistributed to the surface of cocultured oligodendrocytes. After invasion of macrophages to a site of neural injury, enzymes secreted by macrophages can release extracellular stores of fibroblast growth factor into the vicinity. This burst of mitotic potential may preferentially stimulate astrocyte rather than oligodendrocyte division, leading to glial scarring and a subsequent failure of remyelination. Other factors to be considered in the potential for remyelination after injury are astrocyte-derived factors that inhibit myelination and the proteins in oligodendrocytes that prevent axonal regrowth indirectly influencing remyelination potential. Thus, provided the oligodendrocyte can gain access to relevant mitogens either in the axonal plasma membrane or in a soluble form and undergo a wave of proliferation, there is good potential for remyelination after neural injury. However, if axonal regrowth is inhibited and astrocytes preferentially are stimulated to divide and form a glial scar, the prognosis for remyelination is poor.