Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland, OR 97201-3098, USA Department of Cell Biology and Anatomy, Oregon Health Sciences University, Portland, OR 97201-3098, USA.
Restor Neurol Neurosci. 1994 Jan 1;6(4):287-96. doi: 10.3233/RNN-1994-6404.
Regeneration of peripheral nerve fibers over long distances often requires extended periods of convalescence. Loss to society can be measured in terms of increased health care costs, decreased productivity and, in the case of job-related injuries, larger workers' compensation claims. The availability of drugs to increase axonal regeneration would be beneficial not only to patients but also to society in general by decreasing these costs. In the present paper, we present our initial studies on the regenerative effects of the new immunosuppressive agent FK506. Rats given a sciatic nerve crush (axotomy) received daily subcutaneous injections of FK506 (1.0 mg/kg); axotomized control animals received saline. Clinical signs of recovery in the hind feet were manifested two days earlier in FK506-treated than in saline-treated animals; movement in the toes, and walking on the hind feet and toes were observed at 16 and 17 days, respectively, in saline-treated rats and at 14 and 15 days, respectively, in FK506-treated rats. Measurement of interdigit distances in the hind feet at 18 days following axotomy showed a return toward normal position of the toes (increased interdigit distances) during walking in FK506-treated rats. Light and electron microscopy performed at 18 days following axotomy confirmed the clinical appearance of increased functional recovery in FK506-treated rats. Distal to the crush site, the sciatic nerve and its terminal branches from FK506-treated animals contained more myelinated fibers compared to saline-treated animals; in the soleus nerve, the numbers of myelinated axons was increased 2.75-fold. Taken together, the present results suggest that FK506 enhances recovery of function in the rat by increasing the rate of axonal regeneration following a sciatic nerve crush.
外周神经纤维的长距离再生通常需要长时间的康复期。从增加的医疗保健费用、生产力下降以及与工作相关的伤害导致的更大的工人赔偿要求等方面，可以衡量对社会的损失。提供促进轴突再生的药物不仅对患者，而且对整个社会都有益，因为这可以降低这些成本。在本文中，我们介绍了我们对新型免疫抑制剂 FK506 再生作用的初步研究。接受坐骨神经挤压（轴突切断）的大鼠每天接受 FK506（1.0mg/kg）皮下注射；接受生理盐水的轴突切断对照动物。FK506 治疗的动物比生理盐水治疗的动物更早出现后脚恢复的临床症状；生理盐水治疗的大鼠分别在第 16 天和第 17 天观察到脚趾运动和后脚和脚趾行走，而 FK506 治疗的大鼠分别在第 14 天和第 15 天观察到脚趾运动和后脚和脚趾行走。在轴突切断后 18 天测量后脚的趾间距离，FK506 治疗的大鼠在行走时显示脚趾位置向正常位置（趾间距离增加）恢复。在轴突切断后 18 天进行的光镜和电镜检查证实了 FK506 治疗的大鼠功能恢复增加的临床外观。与生理盐水治疗的动物相比，FK506 治疗的动物在挤压部位远端的坐骨神经及其终末分支包含更多有髓纤维；在比目鱼肌神经中，有髓轴突的数量增加了 2.75 倍。总之，这些结果表明 FK506 通过增加坐骨神经挤压后轴突再生的速度来增强大鼠的功能恢复。
