Storage, metabolism, and processing of 125I-fibroblast growth factor-2 after intracerebral injection

Basic fibroblast growth factor (FGF-2) is a potent trophic agent for both neuronal and non-neuronal cells of the mammalian CNS. It can enhance survival and neurite outgrowth of a variety of neuronal types in vitro and in vivo, and recently has been shown to stimulate neuroblast proliferation in culture. To determine the most effective means of introducing FGF-2 into the brain, and to further our understanding of the behavior of exogenous FGF-2 following intracerebral injection, we examined the diffusion and degradation of 125I-FGF-2 following intraventricular or intraparenchymal injection. SDS-PAGE and autoradiography show that when radiolabelled FGF-2 is injected into the parenchyma of the rat brain, it remains at the site of injection where it is detectable for several days. During this time, it is slowly metabolized to 2 specific heparin-binding metabolic fragments that are virtually identical to the ones described for its metabolism by neurons and astrocytes in vitro. Microscopic examination and autoradiography of these tissue sections show that within these areas, FGF-2 diffuses throughout the site of injection. Initially, it migrates along adjacent fiber tracts, binds to specific cells and to basement membranes of the microvasculature, but later on it remains associated to basement membranes and non-neuronal cells. Based on its slow clearance and slow rate metabolic degradation, this FGF-2 is presumed to be in a sequestered form and to have limited activity. In contrast, the intraventricular injection of 125I-FGF leads to a rapid clearance, with some binding to ependymal cells lining the ventricles and little translocation into the parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)