Ruigt G S, den Brok M H
Neuropharmacology Department, Organon SDG, Oss, The Netherlands.
Cancer Chemother Pharmacol. 1995;36(6):530-5. doi: 10.1007/BF00685804.
The effect of vincristine on regeneration of rat sural and tibial nerves following a crush lesion of the sciatic nerve was studied in the pinch test. Vincristine locally applied through an osmotic minipump at the site of the lesion dose-dependently retarded regeneration of the tibial and sural nerve at a threshold dose of 5 ng/day, whereas regeneration was blocked at a dose of 200 ng/day. Regeneration of the sural nerve was more sensitive to the retarding effects of vincristine than was regeneration of the tibial nerve. Systemic weekly administration (i.p.) of 1 mg/kg of vincristine for 7 weeks had approximately the same effect as local application of 10-20 ng/day for 1 week. The differences in sensitivity between sural and tibial nerves and the large discrepancy between local and systemic administration are discussed. On the basis of the potent effects of vincristine used at low concentrations, the absence of overt effects of local vincristine on animal behavior and the short time course in which the local vincristine effects are observed, it is concluded that this paradigm is an extremely suitable model for studying vincristine-induced defects of nervous system function. This model may be used for evaluating the neuroprotective effects of neurotrophic agents against vincristine-induced neuropathies.
通过夹捏试验研究了长春新碱对坐骨神经挤压损伤后大鼠腓肠神经和胫神经再生的影响。通过渗透微型泵在损伤部位局部应用长春新碱，在阈值剂量5 ng/天时剂量依赖性地延缓胫神经和腓肠神经的再生，而在200 ng/天时再生被阻断。腓肠神经的再生比胫神经的再生对长春新碱的延缓作用更敏感。每周腹腔注射1 mg/kg长春新碱，共7周，其效果与局部应用10 - 20 ng/天，共1周大致相同。讨论了腓肠神经和胫神经在敏感性上的差异以及局部和全身给药之间的巨大差异。基于低浓度长春新碱的强效作用、局部长春新碱对动物行为无明显影响以及观察到局部长春新碱作用的时间进程较短，得出该模型是研究长春新碱诱导的神经系统功能缺陷的极其合适的模型。该模型可用于评估神经营养剂对长春新碱诱导的神经病变的神经保护作用。
