Soluble factors that promote growth of blood vessels are present in several tissues with active capillary proliferation in vivo but their importance for capillary growth in brain are unknown.
The aim of this project is to determine the role of soluble growth factors in the regulation of the active capillary proliferation that occurs in rat brain during early postnatal development. Capillary endothelium isolated from brain will be used as an in vitro bioassay in the characterization of potent growth activity for these cells already found in rat brain extracts. Factor(s) responsible for this activity will be isolated and characterized using preparative and analytical biochemical separation techniques. Initial characterization will be directed at determining if the activity is due to endothelial cell growth factor (ECGF), a peptide mitogen isolated from bovine brain, that stimulates several types of endothelium. In vivo angiogenic activity of ECGF will be determined by measuring the vascularization of the chick chorioallantoic membrane. Brain ECGF will be measured in rats of different ages to determine if varying levels can account for the active capillary growth in early development. Developmental differences in receptors for ECGF will be studied with receptor-ligand binding assays using brain capillary endothelial cells isolated from rats of various ages. Stimulatory activity in rat brain extracts not accounted for by ECGF will be characterized in the same ways proposed for ECGF. Understanding the mechanisms of capillary growth may lead to the ability to manipulate brain capillary proliferation in diseases where stimulation or arrest of neovascularization could have clinical benefit.
| Robertson, P L; Bruno, G R; Datta, S C (1990) Glutamate-stimulated, guanine nucleotide-mediated phosphoinositide turnover in astrocytes is inhibited by cyclic AMP. J Neurochem 55:1727-33 |
