BASIC FIBROBLAST GROWTH-FACTOR IMPROVES RECOVERY AFTER CHEMICALLY-INDUCED BREAKDOWN OF MYELIN-LIKE MEMBRANES IN PURE OLIGODENDROCYTE CULTURES

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 [I-125]-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 [I-125]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. (C) 1994 Wiley-Liss, Inc.