Immunocytochemical characterization of reactive optic nerve astrocytes andmeningeal cells

Regeneration in the adult central nervous system (CNS) is thought to be ham pered by the lesion-induced activation of astrocytes and meningeal cells an d the consecutive formation of a glial scar. The substrate properties of re active astrocytes differ significantly from their neonatal counterparts, wh ich promote axon growth, but in spite of intensive studies the underlying m olecular changes are still not fully understood. We have used two cell cult ure systems to compare the expression of certain surface molecules on neona tal astrocytes, reactive astrocytes and meningeal cells in vitro. Both, neonatal and reactive adult astrocytes exhibited a very similar expre ssion of growth promoting molecules (NCAM, L1, laminin, fibronectin, DSD-1 proteoglycan) and potential inhibitors (tenascinC, chondroitin sulfate, and NG2-proteoglycan), whereas we could not detect the inhibitory keratan sulf ate on either astrocyte population. In contrast, meningeal cells expressed considerable levels of keratan sulfate, but only minimal amounts of NCAM. I n addition, the much higher expression of extracellular fibronectin around meningeal cells implies an excess formation of extracellular matrix (ECM). In coculture experiments, embryonic retinal ganglion cell (RGC) axons clear ly avoided meningeal cells and instead preferred even reactive adult astroc ytes. Our results suggest that the expression of inhibitory keratan sulfate prote oglycans together with a lack of NCAM and an excess production of ECM may b e responsible for the non-permissiveness of meningeal cells. Compared to re active astrocytes, meningeal cells are even worse a substrate for growing a xons. None of the molecules investigated, however, seems to account for the different substrate properties of neonatal and reactive adult astrocytes. GLIA 26:36-46, 1999. (C) 1999 Wiley-Liss, Inc.