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Injury stimulates outgrowth and motility of oligodendrocytes grown in vitro.

Oligodendrocytes which form myelin within the CNS develop from small, highly motile cells that are largely bipolar into mature cells which extend many processes and which produce myelin membranes around multiple axons. The production of myelin sheaths is thought to anchor mature oligodendrocytes (OLs), limiting their motility. When the brain sustains an injury, OLs do not make a significant effort to remyelinate, a fact attributed to both their lack of proliferation and their inability to migrate or extend processes into areas of injury. To test the motility and growth potential of mature OLs, we have designed an in vitro system in which individual cells can undergo long-term observation. Additionally, cells can be mechanically injured by transection of processes using a low-power laser beam. Both control and injured OLs undergo several types of structural change, including extension and retraction of processes and membranes, as well as changes in process caliber. Some OLs exhibit a high degree of motility, moving several hundred micrometers within days. Rather than interfering with the cells' ability to undergo structural change, injury actually stimulated outgrowth of new processes and motility. Neither injury nor addition of basic fibroblast growth factor (bFGF) increased the rate of OL division. However, bFGF paradoxically caused an increase in uptake of the DNA synthesis marker bromodeoxyuridine and had negative effects on OL survival. The unexpected findings that OLs with a mature phenotype are motile and undergo constant structural modification in vitro and that injury induces certain behaviors suggest that myelin-forming OLs in the brain may be capable of a high degree of plasticity under certain conditions.