Heparan sulfate modifies the effects of basic fibroblast growth factor on glial reactivity

Our previous studies have shown that injection of basic fibroblast growth factor (bFGF) into a brain wound enhances astrocyte hypertrophy and macrophage-microglia proliferation in areas adjacent to the lesion. In the present study, designed to test the effects of co-administration of bFGF and heparan sulfate (HS), rats received injections of 200 ng bFGF, 200 ng bFGF with 50 microg HS, or 50 microg 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 nearest to the wound edge. The combination of bFGF and HS did not increase total glial or astrocyte proliferation. We propose that the observed effects resulted from a greater diffusion of bFGF-HS complex into the brain parenchyma, where it bypassed low-affinity binding sites that would otherwise sequester free bFGF. Our results suggest that bFGF-HS complex, compared to bFGF alone, may gain entry into the brain more readily, reach higher concentrations and be more effective as a neurotrophic agent.