Tanaka N, Sasahara M, Ohno M, Higashiyama S, Hayase Y, Shimada M
Department of Pediatrics, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
Brain Res. 1999 May 8;827(1-2):130-8. doi: 10.1016/s0006-8993(99)01319-0.
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.
在未成熟大鼠脑内研究了肝素结合表皮生长因子样生长因子（HB-EGF）mRNA的神经元表达情况。本研究使用了两种大鼠模型。一种是缺氧缺血（HI）脑损伤模型，另一种是N-甲基-D-天冬氨酸（NMDA）脑内注射模型。前一种模型通过永久性结扎左颈动脉并随后暴露于2小时缺氧环境制成。HI损伤后，通过Northern印迹分析评估HB-EGF mRNA。损伤后3至24小时，结扎侧大脑皮层和海马中HB-EGF的转录水平显著高于未处理大鼠。还使用原位杂交研究了HB-EGF mRNA的空间分布。缺氧后3至24小时，结扎侧神经元细胞质中的杂交信号强烈，但梗死区域可见信号局部减弱。在梗死灶周围的神经元中观察到mRNA表达强烈增加。这些结果表明，新生期HI损伤在缺氧后立即诱导神经元HB-EGF上调。在后一种模型中，脑内注射NMDA也诱导了HB-EGF转录本的立即强烈上调。我们的结果表明，HB-EGF可能通过调节由NMDA受体过度激活介导的神经毒性过程，在HI损伤的未成熟脑中作为一种神经保护因子发挥作用。
