Gold B G, Mobley W C, Matheson S F
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201.
J Neurosci. 1991 Apr;11(4):943-55. doi: 10.1523/JNEUROSCI.11-04-00943.1991.
The neuronal perikaryal response to axonal injury (axon reaction) includes reduction in axonal caliber beginning in the proximal portion of the nerve (somatofugal axonal atrophy), development of nuclear eccentricity, and chromatolysis. The means by which these events are triggered is unknown, but it has been argued that loss of a neurotrophic signal from the target of injured neurons plays a role. To date, the identity of this substance(s) remains unknown. In the present study, we have asked whether NGF normally functions to control axonal caliber of sensory neurons in the L4 and L5 dorsal root ganglia (DRG) of the adult rat. Two approaches were used: (1) NGF was continuously delivered to the proximal stump of a transected sciatic nerve to determine whether NGF administration would prevent the production of somatofugal axonal atrophy; and (2) NGF antisera were administered to normal animals to determine whether NGF deprivation would produce somatofugal axonal atrophy. In the first experiment, 9-week-old rats underwent a unilateral sciatic nerve transection at midthigh, and the proximal stump was connected to an osmotic pump containing either NGF or cytochrome C (as control). At 11 weeks of age, dorsal root fibers in lumbar DRG from the control group appeared smaller in caliber and less circular in shape than fibers from age-matched normal animals. Although smaller than those in normal animals, fibers from the NGF-treated nerves were larger than in axotomized controls. Mean axonal area and shape factor (an index in circularity) were measured and found to be decreased significantly (22% and 15%, respectively) from the control group. Fibers from the NGF-treated nerves were significantly (p less than 0.05) larger in axonal caliber and more circular in shape; mean values were only reduced by 11% and 10%, respectively. Quantitation of neurofilament (NF) numbers revealed that the larger calibers in the NGF-treated nerves result from a greater NF content. NGF treatment did not prevent the atrophy of motor fibers in the proximal ventral root. In the second experiment, 2 antisera to mouse NGF were given daily into the footpad for 11 or 12 d; control animals were given normal goat serum. Quantitation of axonal calibers in the L5 DRG demonstrated that mean axonal area and shape factor were significantly (p less than 0.05) reduced by 14% and 17% respectively. The axoplasm of atrophic fibers demonstrated a paucity of NFs.(ABSTRACT TRUNCATED AT 400 WORDS)
神经元胞体对轴突损伤的反应（轴突反应）包括神经近端（离心性轴突萎缩）轴突直径减小、核偏位以及染色质溶解。引发这些事件的机制尚不清楚，但有人认为受损神经元靶标的神经营养信号丧失起了作用。迄今为止，这种物质的身份仍然未知。在本研究中，我们探讨了神经生长因子（NGF）是否正常发挥功能来控制成年大鼠L4和L5背根神经节（DRG）中感觉神经元的轴突直径。采用了两种方法：（1）将NGF持续输送到切断的坐骨神经近端残端，以确定给予NGF是否能防止离心性轴突萎缩的发生；（2）对正常动物给予NGF抗血清，以确定剥夺NGF是否会导致离心性轴突萎缩。在第一个实验中，9周龄大鼠在大腿中部进行单侧坐骨神经切断，近端残端连接到含有NGF或细胞色素C（作为对照）的渗透泵。在11周龄时，对照组腰段DRG中的背根纤维直径比年龄匹配的正常动物的纤维小，形状也较不规则。虽然比正常动物的纤维小，但接受NGF处理的神经纤维比轴突切断的对照组大。测量了平均轴突面积和形状因子（圆形度指数），发现与对照组相比显著降低（分别降低22%和15%）。接受NGF处理的神经纤维轴突直径显著更大（p<0.05），形状更圆；平均值仅分别降低11%和10%。神经丝（NF）数量的定量分析显示，接受NGF处理的神经纤维直径较大是由于NF含量增加。NGF处理并未防止近端腹根运动纤维的萎缩。在第二个实验中，每天向足垫注射两种小鼠NGF抗血清，持续11或12天；对照动物注射正常山羊血清。L5 DRG中轴突直径的定量分析表明，平均轴突面积和形状因子分别显著降低（p<0.05）14%和17%。萎缩纤维的轴浆显示NF数量减少。（摘要截选至400字）
