Boyd J G, Gordon T
Queen's University, Department of Anatomy and Cell Biology, ON, Kingston, Canada.
Exp Neurol. 2003 Oct;183(2):610-9. doi: 10.1016/s0014-4886(03)00183-3.
In contrast to injuries in the central nervous system, injured peripheral neurons will regenerate their axons. However, axotomized motoneurons progressively lose their ability to regenerate their axons, following peripheral nerve injury often resulting in very poor recovery of motor function. A decline in neurotrophic support may be partially responsible for this effect. The initial upregulation of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) by Schwann cells of the distal nerve stump after nerve injury has led to the speculation that they are important for motor axonal regeneration. However, few experiments directly measure the effects of exogenous BDNF or GDNF on motor axonal regeneration. This study provided the first direct and quantitative evidence that long-term continuous treatment with exogenous GDNF significantly increased the number of motoneurons which regenerate their axons, completely reversing the negative effects of chronic axotomy. The beneficial effect of GDNF was not dose-dependent. A combination of exogenous GDNF and BDNF on motor axonal regeneration was significantly greater than either factor alone, and this effect was most pronounced following long-term continuous treatment. The ability of GDNF, either alone or in combination with BDNF, to increase the number of motoneurons that regenerated their axons correlated well with an increase in axon sprouting within the distal nerve stump. Thus long-term continuous treatment with neurotrophic factors, such as GDNF and BDNF, can be used as a viable treatment to sustain motor axon regeneration.
与中枢神经系统损伤不同，受损的外周神经元会再生其轴突。然而，在周围神经损伤后，被切断轴突的运动神经元逐渐丧失其轴突再生能力，常常导致运动功能恢复极差。神经营养支持的下降可能部分导致了这种效应。神经损伤后，远端神经残端的雪旺细胞最初会上调胶质细胞源性神经营养因子（GDNF）和脑源性神经营养因子（BDNF），这引发了人们对它们对运动轴突再生很重要的猜测。然而，很少有实验直接测量外源性BDNF或GDNF对运动轴突再生的影响。本研究提供了首个直接且定量的证据，即长期持续给予外源性GDNF显著增加了再生轴突的运动神经元数量，完全逆转了慢性轴突切断的负面影响。GDNF的有益作用不依赖剂量。外源性GDNF和BDNF联合对运动轴突再生的作用显著大于单独使用任何一种因子，并且这种作用在长期持续治疗后最为明显。GDNF单独或与BDNF联合增加再生轴突的运动神经元数量的能力，与远端神经残端内轴突发芽的增加密切相关。因此，长期持续给予神经营养因子，如GDNF和BDNF，可以作为维持运动轴突再生的可行治疗方法。
