Klempt M, Klempt N D, Gluckmann P D
Department of Paediatrics, University of Auckland, New Zealand.
Berl Munch Tierarztl Wochenschr. 1993 Dec;106(12):419-23.
Insulin-like growth factors (IGFs) are involved in cell growth and differentiation. In muscle tissue they regulate axonal in growth and maintain the connection. They also play a role in regeneration of the peripheral nerve system. We hypothesized that IGFs might also be important factors in the recovery of central nervous tissue after traumatic damage such as perinatal asphyxia. Our group developed a rat model to mimic the resulting damage and test the changes of expression of IGF-1, -2 and several of their binding proteins. We also examined the influence of exogenous IGF-1 and -2 after asphyxia in the same model. Rats underwent a unilateral ligation of the A. carotis followed by a 15 or 90 min inhalational hypoxia (8% O2). The treatment resulted in a mild or severe damage in the ligated hemisphere with either selective neuronal loss or complete infarction of the volume, respectively. The treatment induced expression of both IGFs and binding protein 2, 3 and 5. Binding protein 1 is not expressed and binding protein 4 is suppressed soon after hypoxia-ischemia. We conclude that both IGFs and several of their binding proteins are involved in response and wound healing after hypoxic brain damage. This was further tested in a second experiment. Rats were injected with IGF-1 or IGF-2 intra-ventricular soon after the hypoxic damage. IGF-1 treatment significantly reduced neuronal loss, IGF-2 had no effect. Behaviour tests, however, showed no difference between IGF-1 treated rats and controls. Our studies show interesting aspects for further investigation and a possible treatment of perinatal asphyxia and traumatic damage of nerve tissue.
胰岛素样生长因子(IGFs)参与细胞生长和分化。在肌肉组织中,它们调节轴突向内生长并维持连接。它们还在周围神经系统的再生中发挥作用。我们推测,胰岛素样生长因子可能也是围产期窒息等创伤性损伤后中枢神经组织恢复的重要因素。我们的研究小组建立了一个大鼠模型来模拟由此产生的损伤,并测试IGF-1、-2及其几种结合蛋白的表达变化。我们还在同一模型中研究了窒息后外源性IGF-1和-2的影响。大鼠接受单侧颈动脉结扎,然后进行15或90分钟的吸入性缺氧(8%氧气)。该处理分别导致结扎半球出现轻度或重度损伤,伴有选择性神经元丢失或整个区域完全梗死。该处理诱导了两种胰岛素样生长因子以及结合蛋白2、3和5的表达。缺氧缺血后不久,结合蛋白1不表达,结合蛋白4被抑制。我们得出结论,胰岛素样生长因子及其几种结合蛋白都参与了缺氧性脑损伤后的反应和伤口愈合。在第二个实验中对此进行了进一步测试。缺氧损伤后不久,给大鼠脑室内注射IGF-1或IGF-2。IGF-1治疗显著减少了神经元丢失,IGF-2则没有效果。然而,行为测试显示,接受IGF-1治疗的大鼠与对照组之间没有差异。我们的研究显示了一些有趣的方面,有待进一步研究以及对围产期窒息和神经组织创伤性损伤进行可能的治疗。