Abstract
In addition to the well-known teratogenic effect of thalidomide, previous studies have revealed mild immunosuppressive properties and, more recently, and antiangiogenic activity. To find out more about the specificity of these effects we studied the influence of orally administered thalidomide on Wallerian degeneration in rats. Wallerian degeneration is a potent experimental model for studying reproducible cell proliferation in vivo. Examination of distal nerve segments of transected sciatic nerves from rats that had been treated with thalidomide (2×250 mg/kg per day) revealed a significant reduction of endoneurial cell counts at 10–15 days after surgery compared to that seen in controls. This effect was not statistically significant, at a very early stage of Wallerian degeneration, i.e., at 5 days after transection of the nerve. Subperineurial edema and phagocytosis was also reduced, although this was not statistically significant. This apparently nonspecific inhibitory effect of thalidomide during early Wallerian degeneration shown in the present study should be investigated further for its possible relationship to other previously established inhibitory activities of thalidomide, especially its immunosuppressive effect in man.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abercrombie M, Johnson ML (1946) Quantitative histology of Wallerian degeneration. I. Nuclear populaion in-rabbit sciatic nerve. J Anat 80: 37–50
Barnes PF, Chatterjee D, Brennan PJ, Rea TH, Modlin RL (1992) Tumor necrosis factor production in patients with leprosy. Infect Immun 60: 1441–1446
Beuche W, Friede RL (1984) The role of non-resident cells in Wallerian degeneration. J Neurocytol 13: 767–796
D'Amato RJ, Loughnan MS, Flynn E, Folkman J (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 91: 4082–4085
De Iongh RU (1990) A quantitative ultrastructural study of motor and sensory lumbosacral nerve roots in the thalidomidetreated rabbit fetus. J Neuropathol Exp Neurol 49: 564–581
Griffin JW, George R, Lobato C, Tyor WR, Yan LC, Glass JD (1992) Macrophage responses and myelin clearance during Wallerian degeneration: relevance to immune-mediated demyelination. J Neuroimmunol 40: 153–166
Günzler V (1992) Thalidomide in human immunodeficiency virus (HIV) patients. A review of safety considerations. Drug Safety 7: 116–134
Krücke W, Hartrott HH von, Schröder ET, Gibbels E, Scheid W (1971) Licht-und elektronenmikroskopische Untersuchungen zum Spätstadium der Thalidomidneuropathie. Fortscher Neurol Psychiatr 39: 15–50
Makonkawkeyoon S, Limson-Pobre RN, Moreira AL, Schauf V, Kaplan G (1993) Thalidomide inhibits the replication of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 90: 5974–5978
Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G (1993) Thalidomide exerts its inhibitory action ontumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 177: 1675–1680
Sampaio EP, Moreira AL, Sarno EN, Malta AM, Kaplan G (1992) Prolonged treatment with recombinant interferon gamma induces crythema nodosum leprosum in lepromatous leprosy patients. J Exp Med 175: 1729–37
Sampaio EP, Kaplan G, Miranda A, Nery JA, Miguel CP, Viana SM, Sarno EN (1993) The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. J Infect Dis 168: 408–414
Schröder JM, Gibbels E (1977) Marklose Nervenfasern im Senium und im Spätstadium der Thalidomid-Polyneuropathie: quantitativ-elektronenmikroskopische Untersuchungen. Acta Neuropathol (Berl) 39: 271–280
Schröder JM, Matthiesen T (1985) Experimental thalidomide neuropathy: the morphological correlate of reduced conduction velocity. Acta Neuropathol (Berl) 65: 285–292
Schröder JM, Sellhaus B, Wöhrmann T, Kögel B, Zwingenberger K (1994) Cytostatic and anti-edematous effects of thalidomide during early Wallerian degeneration (abstract). Clin Neuropathol 5: 269–270
Seiler N, Schröder JM (1970) Beziehungen zwischen Polyaminen und Nucleinsäuren. II. Biochemische und feinstrukturelle Untersuchungen am peripheren Nerven während der Wallerschen Degeneration. Brain Res 22: 81–103
Shannon EJ, Ejigu M, Haile-Mariam HS, Berhan TY, Tasesse G (1992) Thalidomide's effectiveness in erythema nodosum leprosum is associated with a decrease in CD4+ cells in the peripheral blood. Lepr Rev 63: 5–11
Stoll G, Griffin JW, Li Cy, Trapp BD (1989) Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol 18: 671–683
Author information
Authors and Affiliations
Additional information
The results of this study were presented in part at the First Meeting of the Peripheral Nerve Society, 12-16 June 1994, in St. Paul, Minn., USA, and at the 39th Annual Meeting of the Deutsche Gesellschaft für Neuropathologie and Neuroanatomie, 5–8 October 1994, in München, Germany [15]
Rights and permissions
About this article
Cite this article
Schröder, J.M., Sellhaus, B., Wöhrmann, T. et al. Inhibitory effects of thalidomide on cellular proliferation, endoneurial edema and myelin phagocytosis during early Wallerian degeneration. Acta Neuropathol 89, 415–419 (1995). https://doi.org/10.1007/BF00307645
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00307645