Skip to main content
SpringerLink
Log in

Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

We performed a morphological, morphometric and toxicological study on the spinal ganglia and peripheral nerves of the rat after chronic administration of cisplatin (cis-dichlorodiammineplatinum II; DDP) with two different schedules. Severe damage of the spinal ganglia neurons was demonstrated with predominant involvement of the nucleus and nucleolus associated with a decrease in the cell size. Morphological and morphometric changes also occurred in the sciatic and peroneal nerves with the features of axonopathy. All these changes were more marked in the group of rats which underwent the most intense DDP treatment and the tissue platinum concentrations were also higher in this group. This experimental model is the first available for chronic DDP administration in which concomitant spinal ganglia and peripheral nerve damage has been confirmed pathologically. Our study supports the hypothesis that DDP-induced peripheral nerve fiber degeneration may result from nuclear and nucleolar changes in the sensory ganglion cell perikaryon.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Asbury AK (1984) Uremic neuropathy. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 2nd edn. Saunders, Philadelphia, pp 1811–1825

    Google Scholar 

  2. Ashraf M, Riggs JE, Wearden S, Scotchel P (1990) Prospective study of nerve conduction parameters and serum magnesium following cisplatin therapy. Gynecol Oncol 37:29–33

    Google Scholar 

  3. Boogered W, Bokkel Huinink WW, Dalesio O, Hoppenbrouwers WJJF, van der Sande J (1990) Cisplatin induced neuropathy: central, peripheral and autonomic nerve involvement. J Neuroncol 9:255–263

    Google Scholar 

  4. Cavaletti G, Tredici G, Pizzini G, Minoia A (1990) Tissue platinum concentration and cisplatin schedules. Lancet 336:1003

    Google Scholar 

  5. Cavaletti G, Petruccioli MG, Tredici G, Marmiroli P, Barajon I, Fabbrica D, Di Francesco A (1991) Effects of repeated administration of low doses of cisplatin on the rat nervous system. Int J Tissue React 13:151–157

    Google Scholar 

  6. Cavaletti G, Marzorati L, Bogliun G, Colombo N, Marzola M, Pittelli MR, Tredici G (1992) Cisplatin peripheral neurotoxicity is not only total dose but also single dose intensity-dependent. Cancer 69:203–207

    Google Scholar 

  7. Clark AW, Parhad IM, Griffin JW, Price DL (1980) Neurotoxicity of cis-platinum: pathology of the central and peripheral nervous system. Neurology 30:429

    Google Scholar 

  8. Cho ES, Spencer PS, Jortner BS (1980) Doxorubicin. In: Spencer PS, Schaumburg HH (eds) Experimental and clinical neurotoxicology. William & Wilkins, Baltimore, pp 430–439

    Google Scholar 

  9. Cornblath DR, Brown MJ (1988) Influence of malnutrition on developing rat peripheral nerves. Exp Neurol 99:403–411

    Google Scholar 

  10. Daugaard GK, Petrera J, Trojaborg W (1987) Electrophysiological study of the peripheral and central neurotoxic effect of cis-platin. Acta Neurol Scand 76:86–93

    Google Scholar 

  11. De Konig P, Neijt JP, Jennekens FG, Gispen WH (1987) Evaluation of cis-diammine dichloroplatinum (II) (cisplatin) neurotoxicity in rats. Toxicol Appl Pharmacol 89:81–87

    Google Scholar 

  12. De Konig P, Neijt JP, Jennekens FG, Gispen WH (1987) Org. 2766 protects from cisplatin-induced neurotoxicity in rats. Exp Neurol 97:746–750

    Google Scholar 

  13. Fakan S, Hernandez-Verdun D (1986) The nucleolus and the nucleolar organizer regions. Biol Cell 56:189–206

    Google Scholar 

  14. Gastaut JL, Pellissier JF (1985) Neuropathie au cisplatine. Etude clinique, electrophysiologique et morfologique. Rev Neurol (Paris) 141:614–626

    Google Scholar 

  15. Gerritsen van der Hoop R, Neijt JP, Jennekens FGI, Gispen WH (1989) Protection from cisplatin induced neuropathy in rats by the ACTH (4–9) analogue Org. 2766. In: Pleasure D, Fiori M, Scarlato G, Scarpini E (eds) Peripheral nerve development and regeneration. Livinia, Padova, pp 145–148

    Google Scholar 

  16. Gunderson HJG (1977) Notes on the estimation of numerical density of arbitrary profiles: the edge effect. J Microsc 111:219–223

    Google Scholar 

  17. Hadley D, Herr HW (1979) Peripheral neuropathy associated with cis-dichlorodiammineplatinum (II) treatment. Cancer 44:2026–2028

    Google Scholar 

  18. Jennekens FGI (1987) Peripheral neuropathy in renal and hepatic insufficency. Handb Clin Neurol 51:355–366

    Google Scholar 

  19. Kedar A, Cohen ME, Freeman AI (1978) Peripheral neuropathy as a complication of cis-dichlorodiammineplatinum (II) treatment: a case report. Cancer Treat Rev 62:819–821

    Google Scholar 

  20. Lippard SJ (1982) New chemistry of an old molecule. Science 218:1075–1085

    Google Scholar 

  21. Mollman JE (1990) Cisplatin neurotoxicity. N Engl J Med 322:126–127

    Google Scholar 

  22. Muller LJ, Gerritsen van der Hoop R, Moore-van Delft C, Gispen WH, Roubos EW (1990) Morphological and electrophysiological study of the effects of cisplatin and Org. 2766 on rat spinal ganglion neurons. Cancer Res 50:2437–2442

    Google Scholar 

  23. Olsson Y (1984) Vascular permeability in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 2nd edn. Saunders, Philadelphia, pp 579–597

    Google Scholar 

  24. Parti R, Wolf W (1990) Quantitative subcellular distribution of platinum in rats tissues following i.v. bolus and i.v. infusion of cisplatin. Cancer Chemother Pharmacol 26:188–192

    Google Scholar 

  25. Riggs JE, Ashraf M, Snyder RD, Gutmann L (1988) Prospective nerve conduction studies in cisplatin therapy. Ann Neurol 23:92–94

    Google Scholar 

  26. Roelofs RI, Hrushesky W, Rogin J, Rosenberg L (1984) Peripheral sensory neuropathy and cisplatin chemotherapy. Neurology 34:934–938

    Google Scholar 

  27. Rosenberg B (1985) Fundamental studies with cisplatin. Cancer 55:2303–2316

    Google Scholar 

  28. Schmalbruch H (1987) The number of neurons in dorsal root ganglia L4–L6 of the rat. Anat Rec 219:315–322

    Google Scholar 

  29. Spencer PS, Schaumburg HH (1984) Experimental models of primary axonal disease induced by toxic chemicals. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 2nd edn. Saunders, Philadelphia, pp 636–649

    Google Scholar 

  30. Spencer PS, Thomas PK (1974) Ultrastructural studies of the dying-back process. II. The sequestration and removal by Schwann cells and oligodendrocytes of organelles from normal and diseased axons. J Neurocytol 3:763–770

    Google Scholar 

  31. Terheggen PMAB, Gerritsen van der Hoop R, Floot BGJ, Gispen WH (1989) Cellular distribution of cis-diaminedichloroplatinum (II)-DNA binding in rat dorsal root spinal ganglia: effect of the neuroprotecting peptide Org. 2766. Toxicol Appl Pharmacol 99:334–343

    Google Scholar 

  32. Thompson SW, Dawis LE, Kornfield M, Hilgers RD, Standefer JC (1984) Cisplatin neuropathy: clinical, electrophysiologic, morphologic, and toxicologic studies. Cancer 54:1269–1275

    Google Scholar 

  33. Tomiwa K, Nolan C, Cavanagh JB (1986) The effect of cisplatin on the rat spinal ganglia: a study by light and electron microscopy and by morphometry. Acta Neuropathol (Berl) 69:295–308

    Google Scholar 

  34. Tredici G, Di Francesco A, Cavaletti G (1990) Utilization of automatic image analysis and PC data elaboration in studying peripheral nerves. J Neurol [Suppl] 237:S42

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Monza

    G. Cavaletti

  2. Institute of Human Anatomy, University of Milan, v. Mangiagalli 31, I-20133, Milan, Italy

    G. Tredici, P. Marmiroli, M. G. Petruccioli, I. Barajon & D. Fabbrica

Authors
  1. G. Cavaletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Tredici
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Marmiroli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. G. Petruccioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. Barajon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Fabbrica
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by the grant no. 91.00220.PF41 from the Italian National Research Council (CNR)-targeted project “Prevention and control disease factors”

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cavaletti, G., Tredici, G., Marmiroli, P. et al. Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats. Acta Neuropathol 84, 364–371 (1992). https://doi.org/10.1007/BF00227662

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00227662

Key words

Search

Navigation