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

1.利用从大鼠胎儿中获得的原代神经元培养物进行体外模型研究，我们发现中度缺氧应激可使神经元耐受随后的严重缺氧，并且bFGF参与了这一机制（Neurosci Res, 1995）2。已知生长抑制因子（GIF）抑制培养神经元的神经突伸长，并在成熟的大脑中组成性地表达。面神经横断后，GIF mRNA在横断后第3天减少，并持续抑制至第5周（Mol Brain Res, 1995）。此外，我们通过各种损伤模型表明，GIF mRNA的表达与面神经的功能状态相关（facial nerve Res, 1994）。相比之下，皮质消融或MCA闭塞模型的研究表明，损伤后1天GIF mRNA表达减少，但在损伤后4天表达增加（J Neurotrauma, 1995, J Cereb Blood Flow Metab, 1995）。局部应用bFGF可增加皮质消融后1天对GIF mRNA的抑制（J Neurotrauma, 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).