Fibroblast growth factor (FGF) levels in the developing rat brain.

Acidic and basic fibroblast growth factors (FGF) are polypeptides with potent multipotential trophic effects on central nervous system (CNS) glia, endothelial cells, and neurons. These factors are characterized by strong binding to heparin, and are commonly assayed by their mitogenic activity on Balb/c 3T3 cells in vitro. We found a marked (ca. 13-fold) increase in Balb/c 3T3 mitogenic activity in the developing rat brain from the embryonic stage to the third postnatal week. High levels were sustained in the mature brain. Most of the mitogenic activity from rat brain bound strongly to heparin-affinity columns, and was eluted at positions characteristic of acidic FGF (aFGF) and basic FGF (bFGF). The presence of aFGF and bFGF in eluted peaks was confirmed by immunoblotting techniques using specific anti-FGF sera. Heparin-affinity high performance liquid chromatography (HPLC) showed a proportionately greater increase in levels of aFGF than bFGF between the tenth and fortieth postnatal days. Increases in FGF levels during late embryonic and early postnatal stages of brain development may play an important role in the glial and capillary proliferation, as well as in the neuronal outgrowth and synapse formation that is occurring during this time. The differential rates of accumulation of aFGF vs bFGF suggest different physiological roles for these factors in the developing brain.

Increased levels of basic fibroblast growth factor (bFGF) following focal brain injury.

Focal injury to the mammalian central nervous system (CNS) results in a cascade of cellular responses - including glial and capillary proliferation and neural sprouting - that contribute to the repair of neural tissue and to the recovery of neurological function. Fibroblast growth factors (FGFs) are heparin-binding polypeptides with potent trophic effects on CNS glia, endothelia, and neurons; both acidic and basic forms are found in the mammalian CNS. We used heparin-affinity chromatography coupled to Balb/c 3T3 mitogenic assay to show a marked increase in levels of bioactive FGFs in tissue surrounding focal cortical lesions of the mature rat brain at one week after injury. Heparin-affinity HPLC showed that this increase was due to a large increase in levels of basic FGF (bFGF), and a much smaller increase in levels of acidic FGF (aFGF) after injury. Increased bFGF bioactivity was paralleled by increased levels of immunoreactive bFGF, as assessed by Western blotting techniques. Increased bFGF levels may play an important role in the cascade of cellular reactions occurring after focal brain injury.