Expression of platelet-derived growth factor B-chain and β-receptor in hypoxic/ischemic encephalopathy of neonatal rats

Expression of platelet-derived growth factor B-chain and of its specific receptor (β-receptor) was investigated in immature brains with hypoxic/ischemic injury. After the left common carotid arteries of seven- day-old rats were ligated and pups were placed in a hypoxic chamber, the protein and messenger RNA of both B-chain and β-receptor were assessed using immunocytochemistry and northern analysis, respectively. Transcripts for B- chain were localized by in situ hybridization. Faint but definite expression of B-chain and β-receptor was seen in the brains of untreated neonatal controls. Three to 48 h after hypoxia B-chain protein was generally increased above control levels, but locally decreased expression was seen in infarcted areas. Enhanced induction of messenger RNA of B-chain was seen in the both sides of cerebral cortices and hippocampi at 3 h. Strongly increased positivity for B-chain protein and mRNA occurred in the neurons surrounding the infarct. In situ hybridization still showed this up-regulation seven days after hypoxia. Beta-receptor protein expression was enhanced in some neurons immediately surrounding the infarct at 3 h of hypoxia, and marked up- regulation was seen at 16 h. Beta-receptor messenger RNA remained at control levels. Immunocytochemistry showed strong immunoreactivity for the β- receptor on the neurons surrounding the infarct at 72 h. These results indicate that a neonatal hypoxic/ischemic insult induces neuronal up- regulation of the platelet-derived growth factor B-chain as well as β- receptor immediately after hypoxia. While this up-regulation is relatively transient in most neurons, sublethal damage to neurons immediately surrounding an infarct induces sustained up-regulation. Through autocrine and paracrine mechanisms, platelet-derived growth factor B-chain molecules may act as a neuroprotective factor in immature brain experiencing with hypoxic/ischemic injury.