title: Expression of platelet-derived growth factor B-chain and beta-receptor in hypoxic/ischemic encephalopathy of neonatal rats.
abstract: Expression of platelet-derived growth factor B-chain and of its specific receptor (beta-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 beta-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 beta-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 focally 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 beta-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 beta-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.
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Sasahara
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Yamano
authors.forename: M
authors.initials: M
authors.lastname: Shimada
authors.forename: F
authors.initials: F
authors.lastname: Hazama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D002534:Hypoxia, Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D046911:Macromolecular Substances; D009474:Neurons / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor