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 r at brain. These cells form myelin-like membranes and were used as a mo del system for toxic attack. A 24 hr treatment with 2.10(-5) M lysopho sphatidylcholine (LPC) induced a loss of 59% of the cells in these cul tures, with a 64% reduction in [I-125]-iododeoxyuridine incorporation compared to untreated controls. An absence of processes and myelin-lik e sheaths was observed in the remaining cells. Numerous intracytoplasm ic inclusions were observed on transmission electron microscopy. Immun ocytochemical studies with A2B5 monoclonal antibody (mAb), which recog nizes oligodendrocyte-type 2 astrocyte (O-2A) precursors, OL-1 mAb (di rected 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 fibro blast growth factor (bFGF) induced reconstruction of myelin-like membr anes, albeit less compacted than in untreated controls. The doubling i n number of cells and the 46% increase in [I-125]iododeoxyuridine inco rporation was due essentially to proliferation of O-2A progenitors. Th ese 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.