Pu S F, Zhuang H X, Marsh D J, Ishii D N
Department of Physiology, Colorado State University, Fort Collins 80523, USA.
J Neurosci Res. 1999 Jan 1;55(1):9-16. doi: 10.1002/(SICI)1097-4547(19990101)55:1<9::AID-JNR2>3.0.CO;2-J.
The prolonged disconnection of nerve from muscle results in the death of motoneurons and permanent paralysis. Because clinical nerve injuries generally involve postbirth motoneurons, there is interest in uncovering factors that may support their survival. A rich history of research dating back to the time of Santiago Ramon y Cajal and Viktor Hamburger supports the inference that there are soluble neurotrophic factors associated with nerve and muscle. However, the endogenous factors normally required for motoneuron survival following nerve injury have eluded identification. Two interrelated hypotheses were tested: (1) administration of insulin-like growth factor-II (IGF-II) can support the survival of postbirth motoneurons, and (2) endogenous IGFs are essential for motoneuron survival following nerve injury. We report that IGF-II locally administered close to the proximal nerve stump prevented the death of motoneurons (estimated by relative numbers of neuronal profiles) which ordinarily follows sciatic nerve transection in neonatal rats. By contrast, anti-IGF antiserum, as well as IGF binding proteins-4 and -6, significantly increased (P < 0.01) motoneuron death. This report shows that IGF-II can support survival, and contains the novel observation that endogenous IGF activity in or near nerves is required for motoneuron survival. Other studies have determined that IGF gene and protein expression are increased in nerve and muscle following sciatic nerve crush, and that IGFs are required for nerve regeneration. Taken together, these data show that IGFs are nerve- and muscle-derived soluble factors that support motoneuron survival as well as nerve regeneration.
神经与肌肉的长期分离会导致运动神经元死亡和永久性麻痹。由于临床神经损伤通常涉及出生后的运动神经元，因此人们对发现可能支持其存活的因素很感兴趣。可追溯到圣地亚哥·拉蒙·伊·卡哈尔和维克托·汉堡时期的丰富研究历史支持了这样的推断，即存在与神经和肌肉相关的可溶性神经营养因子。然而，神经损伤后运动神经元存活通常所需的内源性因子仍未被确定。我们测试了两个相互关联的假设：（1）给予胰岛素样生长因子-II（IGF-II）可以支持出生后运动神经元的存活，以及（2）内源性IGF对神经损伤后运动神经元的存活至关重要。我们报告称，在靠近近端神经残端局部给予IGF-II可防止运动神经元死亡（通过神经元轮廓的相对数量估计），而这种死亡通常会在新生大鼠坐骨神经横断后发生。相比之下，抗IGF抗血清以及IGF结合蛋白-4和-6显著增加（P<0.01）了运动神经元死亡。本报告表明IGF-II可以支持存活，并且包含了一个新的观察结果，即神经内或神经附近的内源性IGF活性是运动神经元存活所必需的。其他研究已经确定，坐骨神经挤压后神经和肌肉中IGF基因和蛋白表达增加，并且IGF对神经再生是必需的。综上所述，这些数据表明IGF是源自神经和肌肉的可溶性因子，可支持运动神经元存活以及神经再生。
