Harding D I, Greensmith L, Connold A L, Vrbová G
Department of Anatomy and Developmental Biology, University College London, U.K.
Neuroscience. 1996 Feb;70(3):799-805. doi: 10.1016/s0306-4522(96)83016-8.
Following sciatic nerve crush at birth the rat soleus muscle is rendered permanently weak. This reduction in muscle force is caused by the loss of a proportion of its motoneurons. Furthermore, motoneurons that survive and reach the muscle fail to reoccupy a sufficient number of denervated muscle fibres to compensate for the loss of neurons. Both the loss of motoneurons and poor reinnervation may be due to the inability of the regenerating axons to establish and maintain neuromuscular contacts. Application of leupeptin, an inhibitor of a calcium-activated neutral protease and some serine proteases, is known to help in the maintenance of neuromuscular contacts during development and axonal sprouting. Here we examined whether protecting new neuromuscular contacts formed between regenerating axons and denervated muscle fibres after nerve injury, would influence the survival of motoneurons and improve muscle recovery. This study shows that in muscles treated with leupeptin the reduction in weight and force output after nerve crush at birth was significantly less than in those that were untreated. Moreover, the number of motor units in the leupeptin-treated muscles was significantly higher than in untreated muscles. Thus, treating regenerating nerve terminals with leupeptin during early stages of reinnervation rescues motoneurons and improves muscle recovery.
出生时坐骨神经受到挤压后，大鼠比目鱼肌会永久性变弱。肌肉力量的这种下降是由于一部分运动神经元的丧失所致。此外，存活并到达肌肉的运动神经元未能重新支配足够数量的失神经支配的肌纤维，以补偿神经元的损失。运动神经元的丧失和再支配不佳可能都是由于再生轴突无法建立和维持神经肌肉联系。已知亮抑蛋白酶肽（一种钙激活中性蛋白酶和一些丝氨酸蛋白酶的抑制剂）在发育和轴突萌发过程中有助于维持神经肌肉联系。在此，我们研究了保护神经损伤后再生轴突与失神经支配的肌纤维之间形成的新神经肌肉联系是否会影响运动神经元的存活并改善肌肉恢复。这项研究表明，在出生时神经挤压后用亮抑蛋白酶肽处理的肌肉中，重量和力量输出的下降明显小于未处理的肌肉。此外，用亮抑蛋白酶肽处理的肌肉中的运动单位数量明显高于未处理的肌肉。因此，在再支配的早期阶段用亮抑蛋白酶肽处理再生神经末梢可挽救运动神经元并改善肌肉恢复。
