HEPARAN-SULFATE MODIFIES THE EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR ON GLIAL REACTIVITY

Our previous studies have shown that injection of basic fibroblast gro wth factor (bFGF) into a brain wound enhances astrocyte hypertrophy an d macrophage-microglia proliferation in areas adjacent to the lesion. In the present study, designed to test the effects of co-administratio n of bFGF and heparan sulfate (HS), rats received injections of 200 ng bFGF, 200 ng bFGF with 50 mu g HS, or 50 mu g HS into a brain wound. Glial proliferation and astrocyte hypertrophy were evaluated in seven non-overlapping subfields in the mid-cortex including the wound edge. Our results show that bFGF-HS, compared to bFGF or HS alone, enhanced the total area of GFAP staining in all subfields except the one neares t to the wound edge. The combination of bFGF and HS did not increase t otal glial or astrocyte proliferation. We propose that the observed ef fects resulted from a greater diffusion of bFGF-HS complex into the br ain parenchyma, where it bypassed low-affinity binding sites that woul d otherwise sequester free bFGF. Our results suggest that bFGF-HS comp lex, compared to bFGF alone, may gain entry into the brain more readil y, reach higher concentrations and be more effective as a neurotrophic agent. (C) 1997 Elsevier Science B.V.