Heparin-binding epidermal growth factor-like growth factor mRNA expression in neonatal rat brain with hypoxic ischemic injury

The neuronal expression of mRNA of heparin-binding epidermal growth factor-like growth factor (HB-EGF) was investigated in immature rat brains. Two rat models were used in this study. One was a hypoxic/ischemic (HI) brain injury model, and the other was an N-methyl-D-aspartate (NMDA) intracerebral injection model. The former model was made by permanent ligation of the left carotid artery and subsequent exposure to 2 h of hypoxia. After the HI insult, the HB-EGF mRNA was assessed by a Northern blot analysis. The levels of transcripts for HB-EGF in the cerebral cortex and the hippocampus of the ligated side were significantly higher than those of non-treated rats from 3 to 24 h after the insult. The spatial distribution of the mRNA of HB-EGF was also studied using in situ hybridization. Three to 24 h after the hypoxia, hybridization signals were intense in neuronal cytoplasm on the ligated side, but a focally decreased signal was seen in infarcted areas. Strongly increased mRNA expression was observed in the neurons surrounding the infarct. These results indicate that a neonatal HI insult induces a neuronal upregulation of HB-EGF immediately after hypoxia. In the latter model, the intracerebral NMDA injection also induced an immediate, strong upregulation of HB-EGF transcripts. Our results indicate that HB-EGF may act as a neuroprotective factor in the immature brain with HI injury by modulating the neurotoxic process which is mediated by overactivation of the NMDA receptor. (C) 1999 Elsevier Science B.V. All rights reserved.