The survival and growth of all nerve cells including those in the brain is thought to be controlled by special growth regulatory proteins, called neuronotrophic factors (NTF). At this time only one NTF has been identified, nerve growth factor, and it only affects a very small proportion of the neurons in the brain. From studies using cell cultures of highly purified nerve cells from fetal rat brains, Dr. Walicke and her collaborators have recently obtained evidence suggesting that two proteins long known to stimulate growth of connective tissue, the fibroblast growth factors (FGF), might also improve neuronal survival and growth. This research will try to determine whether the FGF's are really NTF's for brain neurons. A combination of biochemical and histological techniques will be used to determine whether the FGF's stimulate neurons directly by acting on specific cell receptors. These studies will first use isolated cells in culture, then intact brain tissue. Whether FGF is produced by constituents of brain tissue such as neurons or their support cells (glia) will be studied. Neurons from different regions of the brain will be examined in tissue culture to determine what types of CNS neurons might be stimulated by FGF. Finally, whether application of FGF into a wound in the brain can influence neuronal survival or process growth will be examined. Dr. Walicke has an excellent reputation in the neuronotrophic factor field and is highly qualified to conduct this important research. In addition to determining whether FGF is a NTF, these studies should indicate whether FGF is a reasonable candidate for use in treating brain injuries or diseases.