MOLECULAR BIOLOGICAL INVESTIGATIONS OF STRESS RESPONSE TO NEURONAL INJURY AND DEVELOPMENT OF NEW THERAPEUTIC APPROACH

1.体外模型的研究利用从大鼠胚胎获得的原代培养的神经元，我们发现中度低氧应激使神经元对随后的严重缺氧耐受，并且碱性成纤维细胞生长因子参与了这一机制(Neurosci Res，1995)。2.用体内模型研究生长抑制因子(GIF)可以抑制培养神经元的轴突伸长，并在成熟的脑中结构性表达。面神经横断术后，GIF mRNA在术后3天开始下降，并持续抑制至5周(Mol Brain Res，1995)。此外，我们使用不同的损伤模型证明了GIF mRNA的表达与面神经的功能状态相关(Face Network Res，1994)。相比之下，皮质消融或大脑中动脉闭塞模型的研究表明，GIF mRNA的表达在损伤后1天减少，而在损伤后4天表达增加(J Neurotragation，1995，J Brab血流Metab，1995)。局部应用碱性成纤维细胞生长因子增强了皮质消融后L天时GIF mRNA的抑制作用(J Neurotragation，1995)。

1.Investigations with in vitro modelUsing primary neuronal cultures obtained from rat fetus, we showed that moderate hypoxic stress the neurons tolerant to subsequent severe hypoxia and that bFGF is involved in the mechanism (Neurosci Res, 1995)2.Investigations with in vivo modelGrowth inhibitory factor (GIF) is known to suppress neurite elongation of cultured neurons and expressed constitutively in the matured brain. Following to the facial nerve transection, GIF mRNA reduced 3 days after transection and continued to be suppressed till 5 weeks (Mol Brain Res, 1995). Furthermore, we showed that expression of GIF mRNA correlates to the functional status of the facial nerve using various injury models (Facial Nerve Res, 1994). In contrast, studies with cortical ablation or MCA occlusion model showed that expression of GIF mRNA reduced 1 day after injury but it increased 4 days after injury (J Neurotrauma, 1995, J Cereb Blood Flow Metab, 1995). Local application of bFGF increased the suppression of GIF mRNA at l day after cortical ablation (J Neurotrauma, 1995).