Boyd J Gordon, Gordon Tessa
Department of Anatomy and Cell Biology, Queen's University, Kingston, ON, Canada.
Mol Neurobiol. 2003 Jun;27(3):277-324. doi: 10.1385/MN:27:3:277.
Over a half a century of research has confirmed that neurotrophic factors promote the survival and process outgrowth of isolated neurons in vitro. The mechanisms by which neurotrophic factors mediate these survival-promoting effects have also been well characterized. In vivo, peripheral neurons are critically dependent on limited amounts of neurotrophic factors during development. After peripheral nerve injury, the adult mammalian peripheral nervous system responds by making neurotrophic factors once again available, either by autocrine or paracrine sources. Three families of neurotrophic factors were compared, the neurotrophins, the GDNF family of neurotrophic factors, and the neuropoetic cytokines. Following a general overview of the mechanisms by which these neurotrophic factors mediate their effects, we reviewed the temporal pattern of expression of the neurotrophic factors and their receptors by axotomized motoneurons as well as in the distal nerve stump after peripheral nerve injury. We discussed recent experiments from our lab and others which have examined the role of neurotrophic factors in peripheral nerve injury. Although our understanding of the mechanisms by which neurotrophic factors mediate their effects in vivo are poorly understood, evidence is beginning to emerge that similar phenomena observed in vitro also apply to nerve regeneration in vivo.
半个多世纪的研究证实，神经营养因子可促进体外分离神经元的存活和轴突生长。神经营养因子介导这些促存活效应的机制也已得到充分阐明。在体内，外周神经元在发育过程中严重依赖有限量的神经营养因子。外周神经损伤后，成年哺乳动物外周神经系统会通过自分泌或旁分泌来源再次提供神经营养因子来做出反应。对三类神经营养因子进行了比较，即神经营养素、胶质细胞源性神经营养因子家族和神经生成性细胞因子。在对这些神经营养因子介导其效应的机制进行总体概述之后，我们回顾了轴突切断的运动神经元以及外周神经损伤后远端神经残端中神经营养因子及其受体的表达时间模式。我们讨论了来自我们实验室和其他实验室的近期实验，这些实验研究了神经营养因子在外周神经损伤中的作用。尽管我们对神经营养因子在体内介导其效应的机制了解甚少，但已有证据开始表明，在体外观察到的类似现象也适用于体内神经再生。
