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Expression of platelet-derived growth factor B-chain and beta-receptor in hypoxic/ischemic encephalopathy of neonatal
M Ohno1, M Sasahara, S Narumiya
1Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan.
Insights
Platelet-derived growth factor B-chain and its receptor are upregulated in immature brains following hypoxic-ischemic injury. This suggests a potential neuroprotective role for platelet-derived growth factor B-chain in neonatal brain injury.
Area of Science:
- Neuroscience
- Developmental Biology
- Pathology
Background:
- Neonatal hypoxic-ischemic (HI) injury is a significant cause of brain damage.
- Platelet-derived growth factor B-chain (PDGF-BB) and its receptor (PDGFR-beta) play roles in cell growth and survival.
- The role of PDGF-BB signaling in immature brain injury is not fully understood.
Purpose of the Study:
- To investigate the expression of PDGF-BB and PDGFR-beta in neonatal rat brains after hypoxic-ischemic injury.
- To determine the temporal and spatial patterns of PDGF-BB and PDGFR-beta expression in response to injury.
- To explore the potential neuroprotective role of PDGF-BB signaling in neonatal brain injury.
Main Methods:
- Neonatal rats (seven days old) underwent ligation of the left common carotid artery followed by hypoxia.
- Immunocytochemistry was used to assess protein expression of PDGF-BB and PDGFR-beta.
- Northern blot analysis and in situ hybridization were employed to evaluate messenger RNA (mRNA) levels.
- Expression patterns were analyzed at various time points post-hypoxia (3-72 hours).
Main Results:
- PDGF-BB and PDGFR-beta showed low expression in control neonatal brains.
- Hypoxic-ischemic injury led to increased PDGF-BB protein and mRNA in cerebral cortices and hippocampi.
- Neurons surrounding the infarct exhibited strong, sustained upregulation of PDGF-BB and PDGFR-beta.
- PDGFR-beta mRNA levels remained largely unchanged, suggesting post-transcriptional regulation.
Conclusions:
- Neonatal hypoxic-ischemic insult induces neuronal upregulation of PDGF-BB and PDGFR-beta.
- Sustained upregulation in neurons near the infarct suggests a role in response to sublethal damage.
- PDGF-BB may act as a neuroprotective factor in immature brains experiencing hypoxic-ischemic injury via autocrine and paracrine mechanisms.
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.