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Retardation of rat sciatic nerve regeneration after local application of minute doses of vincristine

Cancer Chemotherapy and Pharmacology volume 36, pages 530–535 (1995)Cite this article

Abstract

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.

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References

  1. Bisby MA (1980) Axonal transport of labeled protein and regeneration rate in nerves of streptozocin-diabetic rats. Exp Neurol 69: 74

    Google Scholar 

  2. Bradley WG, Lassman LP, Pearce GW, Walton JN (1970) The neuromyopathy of vincristine in man. Clinical, electrophysiological and pathological studies. J Neurol Sci 10: 107

    Google Scholar 

  3. Caccia MR, Comotti B, Ubiali E, Lucchetti A (1977) Vincristine polyneuropathy in man. A clinical and electrophysiological study. J Neurol 216: 21

    Google Scholar 

  4. Casey EB, Jellife AM, LeQuesne PM, Millett YL (1973) Vincristine neuropathy, clinical and electrophysiological observations. Brain 96: 69

    Google Scholar 

  5. Castle MC, Margileth DA, Oliverio VT (1976) Distribution and excretion of3H]vincristine in the rat and dog. Cancer Res 36: 3684

    Google Scholar 

  6. Clarke JTR, Karpati GK, Carpenter S, Wolfe LS (1972) The effect of vincristine on skeletal muscle in the rat. J Neuropathol Exp Neurol 31: 247

    Google Scholar 

  7. Davis RE, Schlumpf BE, Klinger PD (1985) Comparative neurotoxicity of tubulin-binding drugs' inhibition of goldfish carassius-auratus optic nerve regeneration. Toxicol Appl Pharmacol 80: 308

    Google Scholar 

  8. Dehen H (1982) Etude clinique et electrophysiologique de l'isaxonine dans les paralysies facialis peripheriques. Nouv Presse Med 11: 1262

    Google Scholar 

  9. Digregorio F, Favaro G, Panozzo C, Fiori MG (1990) Efficacy of ganglioside treatment in reducing functional alterations induced by vincristine in rabbit peripheral nerves. Cancer Chemother Pharmacol 26: 31

    Google Scholar 

  10. Goldschmidt RB, Steward O (1989) Comparison of the neurotoxic effects of colchicine, the vinca alkaloids, and other microtubule poisons. Brain Res 486: 133

    Google Scholar 

  11. Goldstein BD, Lowndes HE, Cho E (1981) Neurotoxicology of vincristine in the cat. Electrophysiological studies. Arch Toxicol 48: 253

    Google Scholar 

  12. Gottschalk PG, Dyck PJ, Kiely JM (1968) Vinca alkaloid neuropathy—nerve biopsy studies in rats and man. Neurology (Minneap) 18: 875

    Google Scholar 

  13. Green LS, Donoso JA, Heller-Bettinger IE, Samson FE (1977) Axonal transport disturbances in vincristine induced peripheral neuropathy. Ann Neurol 1: 255

    Google Scholar 

  14. Griffiths JD, Stark RJ, Ding JC, Cooper IA (1986) Vincristine neurotoxicity enhanced in combination chemotherapy including both teniposide and vincristine. Cancer Treat Rep 70: 519

    Google Scholar 

  15. Guiheneuc P, Ginet J, Grolleau J-Y, Rojouan J (1982) Etude des effets de l'isaconine sur les lesions de degenerescence axonale retrograde induites chez l'homme par la vincristine. Nouv Presse Med 11: 1257

    Google Scholar 

  16. Jenq C-B, Coggeshall RE (1984) Effects of sciatic nerve regeneration on axonal populations in tributary nerves. Brain Res 295: 91

    Google Scholar 

  17. Jenq C-B, Coggeshall RE (1984) Numbers of regenerating axons in parent and tributary peripheral nerves in the rat. Brain Res 295: 100

    Google Scholar 

  18. Kanje M, Skottner A, Lundborg G (1988) Effects of growth hormone treatment on the regeneration of rat sciatic nerve. Brain Res 475: 254

    Google Scholar 

  19. Keane PE, Fournier J, Steinberg R, Gauthier T, Coudé TX, Guzzi U, Soubrié P, Le Fur G (1992) Neurotrophic effects of SR 57746A in a variety of neurodegenerative models in vivo. Br J Pharmacol 106: 52

    Google Scholar 

  20. Konings PNM, Makkink WK, van Delft AML, Ruigt GSF (1994) Reversal NGF of cytostatic drug-induced reduction of neurite outgrowth in rat dorsal ganglia in vitro. Brain Res 640: 195–204

    Google Scholar 

  21. LeQuesne PM, Fowler CJ, Harding AE (1985) A study of the effects of isaxonine on vincristine-induced peripheral neuropathy in man and regeneration following peripheral nerve crush in the rat. J Neurol Neurosurg Psychiatry 48: 933

    Google Scholar 

  22. Levin V (1980) Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23: 682

    Google Scholar 

  23. McLeod JG, Penny R (1969) Vincristine neuropathy: an electrophysiological and histological study. J Neurol Neurosurg Psychiatry 32: 297

    Google Scholar 

  24. Müller LJ, Moorer-van Delft CM, Zijl R, Roubos EW (1988) Snail neurons as a possible model for testing neurotoxic side effects of antitumour agents: paracrystal formation by vinca alkaloids. Cancer Res 48: 7184

    Google Scholar 

  25. Müller LJ, Moorer-van Delft CM, Zijl R, Roubos EW (1990) Use of snail neurons in developing quantitative ultrastructural parameters for neurotoxic side effects of vinca antitumour agents. Cancer Res 50: 1924

    Google Scholar 

  26. Neuman ISA, Heijmen PS, Peters RC, Ruigt GSF (1993) Fish electroreception as a model for vincristine-induced neuropathies and a possible preventive role for Org 2766 treatment. Comp Biochem Physiol 105C: 165

    Google Scholar 

  27. Passouant P, Cadilhac J (1982) Essai de l'isaxonine dans les polyneuvrites ethyliques. Nouv Presse Med 11: 1269

    Google Scholar 

  28. Peyronnard JM, Charron LF, Lavoie J, Messier JP (1986) Motor, sympathetic and sensory innervation of rat skeletal muscles. Brain Res 373: 288

    Google Scholar 

  29. Sahenk Z, Brady ST, Mendell JR (1987) Studies on the pathogenesis of vincristine induced neuropathy. Muscle Nerve 10: 80

    Google Scholar 

  30. Sandler SG, Tobin W, Henderson ES (1969) Vincristine induced neuropathy. A clinical study of fifty leukemic patients. Neurology 19: 367

    Google Scholar 

  31. Schlaepfer WW (1971) Vincristine-induced axonal alterations in rat peripheral nerve. J Neuropathol Exp Neurol 30: 488

    Google Scholar 

  32. Schochet SS, Lampert PW, Earle KM (1968) Neuronal changes induced by intrathecal vincristine sulfate. J Neurol Sci 27: 645

    Google Scholar 

  33. Shiraishi S (1985) Retardation of nerve fiber regeneration following nerve crush injury in experimental vincristine intoxication. Fukuoka Igaku Zasshi Med 76: 461

    Google Scholar 

  34. Shiraishi S, Le-Quesne PM, Gajree T (1985) The effect of vincristine on nerve regeneration in the rat: an electrophysiological study. J Neurol Sci 71: 9

    Google Scholar 

  35. Shiraishi S, Le-Quesne PM, Gajree T, Cavanagh JB (1985) Morphometric effects of vincristine on nerve regeneration in the rat. J Neurol Sci 71: 165

    Google Scholar 

  36. Shiraishi S, Le Quesne PM, Gajree T, Cavanagh JB (1985) Neurotoxic effects of vincristine on nerve regeneration following crush in the rat. Neuropathol Appl Neurobiol 11: 322

    Google Scholar 

  37. Young JZ, Medawar PB (1940) Fibrin suture of peripheral nerves. Measurement of the rate of regeneration. Lancet II: 126

    Google Scholar 

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  1. Neuropharmacology Department, Organon SDG, Room RE2130, POB 20, 5340 BH, Oss, The Netherlands

    Gé S. F. Ruigt & Maria H. C. den Brok

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  1. Gé S. F. Ruigt
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  2. Maria H. C. den Brok
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Ruigt, G.S.F., den Brok, M.H.C. Retardation of rat sciatic nerve regeneration after local application of minute doses of vincristine. Cancer Chemother. Pharmacol. 36, 530–535 (1995). https://doi.org/10.1007/BF00685804

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  • DOI: https://doi.org/10.1007/BF00685804

Key words

  • Pinch test
  • Rat sciatic nerve
  • Vincristine neuropathy