Abstract
The putative role of growth factors in remyelination was investigated in pure oligodendrocyte (OL) secondary cultures derived from newborn rat brain. These cells form myelin-like membranes and were used as a model system for toxic attack. A 24 hr treatment with 2.10(-5) M lysophosphatidylcholine (LPC) induced a loss of 59% of the cells in these cultures, with a 64% reduction in [125I]-iododeoxyuridine incorporation compared to untreated controls. An absence of processes and myelin-like sheaths was observed in the remaining cells. Numerous intracytoplasmic inclusions were observed on transmission electron microscopy. Immunocytochemical studies with A2B5 monoclonal antibody (mAb), which recognizes oligodendrocyte-type 2 astrocyte (O-2A) precursors, OL-1 mAb (directed against cell surface sulfatides), and anti-myelin basic protein (anti-MBP) antibody showed that the entire OL lineage was affected at all stages of maturation. A 3 day treatment with 10 ng/ml basic fibroblast growth factor (bFGF) induced reconstruction of myelin-like membranes, albeit less compacted than in untreated controls. The doubling in number of cells and the 46% increase in [125I]-iododeoxyuridine incorporation was due essentially to proliferation of O-2A progenitors. These results indicate that if bFGF release occurs during demyelination, it may participate in myelin repair mechanisms in the central nervous system.
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