Summary
The ultrastructure of peripheral sensory nerves was investigated in adult Wistar rats suffering from experimental diabetes mellitus 6 and 10 weeks after the injection of streptozotocin. Giant axons were seen in sections from the nerves of streptozotocintreated rats; some contained masses of neurofilaments, others were predominantly filled with ill-defined vesicles. At the swollen axons, the myelin sheath was thinned or absent. In other regions, large intramyelinic vacuoles were observed. A number of nerve fibers broke down completely and underwent Wallerian degeneration. This was accompanied by Schwann cell proliferation and formation of Büngner bands. Concomitantly with axonal degeneration, nerve regeneration started from intact internodes. The pathomorphology of streptozotocin diabetic neuropathy closely resembles that of some toxic distal axonopathies. This points to a common metabolic basis of giant axonopathies of different etiology.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Asbury AK, Gale MK, Cox SC, Baringer JR, Berg BO (1972) Giant axonal neuropathy: a unique case with segmental neurofilamentous masses. Acta Neuropathol (Berl) 20:237–247
Asbury AK, Nielsen SL, Telfer R (1974) Glue sniffing neuropathy. J Neuropathol Exp Neurol 33:191
Bestetti G, Rossi GL, Zemp D (1981) Changes in peripheral nerves of rats four months after induction of streptozotocin diabetes. Acta Neuropathol (Berl) 54:129–134
Bisby MA (1980) Axonal transport of labelled protein and regeneration rate in nerves of streptozotocin diabetic rats. Exp Neurol 69:74–84
Bischoff A (1967) The ultrastructure of tri-orthocresyl phosphate poisoning. I. Studies on myelin and axonal alterations in the sciatic nerve. Acta Neuropathol (Berl) 9:158–174
Bischoff A (1970) The ultrastructure of tri-orthocresyl phosphate poisoning in the chicken. II. Studies on spinal cord alterations. Acta Neuropathol (Berl) 15:142–155
Bouldin TW, Cavanagh JB (1979) Organophosphorous neuropathy. II A fine-structural study of the early stages of axonal degeneration. Am J Pathol 94:253–270
Brimijoin WS (1982) Abnormalities of axonal transport. Are they a cause of peripheral nerve disease? Mayo Clin Proc 57:707–714
Brimijoin WS (1984) The role of axonal transport in nerve disease. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 2nd edn, WB Saunders, Philadelphia, pp 477–493
Brown MJ, Sumner AJ, Greene DA, Diamond SM, Asbury AK (1980) Distal neuropathy in experimental diabetes mellitus. Ann Neurol 8:168–178
Chokroverty S, Seiden D, Navidad P, Cody R (1988) Distal axonopathy in streptozotocin diabetes in rats. Experientia 44:444–446
Clark HB, Schmidt RE (1984) Identification of dystrophic sympathetic neurons in experimental diabetic autonomic neuropathy. Brain Res 293:390–395
Colombi A, Maroni M, Picchi O, Rota E, Castano P, Foa V (1981) Carbon disulphide neuropathy in rats. A morphological and ultrastructural study of degeneration and regeneration. Clin Toxicol 18:1463–1474
Duckett S, Williams N, Francis S (1974) Peripheral neuropathy associated with inhalation of methyl n-butyl ketone. Experientia 30:1283–1284
Eliasson SG (1964) Nerve conduction changes in experimental diabetes. J Clin Invest 43:2353–2358
Fullerton PM, Barnes JM (1966) Peripheral neuropathy in rats produced by acrylamide. Br J Ind Med 23:210–221
Griffin JW, Hoffman PN, Clark AW, Carroll PT, Price DL (1978) Slow axonal transport of neurofïlament proteins: impairment by β,β′-iminodipropionitrile administration. Science 202:633–635
Griffin JW, Fahnenstock KE, Price DL, Cork LC (1983) Cytoskeletal disorganization induced by local application of bb1-iminodipropionitrile and 2.5-hexanedione. Ann Neurol 14:55–61
Griffin JW, Cork LC, Hoffman PN, Price DL (1984) Experimental models of motor neuron degeneration. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 2nd edn. WB Saunders, Philadelphia, pp 621–635
Hoffman PN, Lasek RJ (1975) The slow component of axonal transport: identification of major structural polypeptides of the axon and their generality among mammalian neurons. J Cell Biol 66:351–366
Hoffman PN, Lasek RJ, Griffin JW, Price DL (1983) Slowing of the axonal transport of neurofilament proteins during development. J Neurosci 3:1694–1700
Hoffman PN, Thompson GW, Griffin JW, Price DL (1985) Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibres. J Cell Biol 101:1332–1340
Hopkins AP (1968) Experimental neuropathy in the baboon. MD thesis, University of London, London
Hopkins AP (1970) The effect of acrylamide on the peripheral nervous system in the baboon. J Neurol Neurosurg Psychiatry 33:805–816
Jakobsen J (1978) Peripheral nerves in early experimental diabetes. Expansion of the endoneurial space to a cause of increased water content. Diabetologia 14:113–119
Jakobsen J, Sidenius P (1980) Decreased axonal transport of structural proteins in streptozotocin diabetic rats. J Clin Invest 66:292–297
Jakobsen J, Brimijoin S, Sidenius P (1983) Axonal transport in neuropathy. Muscle Nerve 6:164–166
Jakobsen J, Sidenius P, Braendgaard H (1986) A proposal for a classification of neuropathies according to their axonal transport abnormalities. J Neurol Neurosurg Psychiatry 49:986–990
Jirmanová I. Lukáš E (1984) Ultrastructure of carbon disulphide neuropathy. Acta Neuropathol (Berl) 63:255–263
Linnoila I, Haltia M, Seppäläinen AM, Palo J (1975) Experimental carbon disulphide poisoning: morphological and neurophysiological studies. In: Környey S, Tariska ST, Gosztonyi G (eds) Proceedings of the VIIth International Congress of Neuropathology. Excerpta Medica, Amsterdam, pp 383–386
Longo FM, Powell HC, Lebeau J, Gerrero MR, Heckman BS, Myers RR (1986) Delayed nerve regeneration in streptozotocin diabetic rats. Muscle Nerve 9:385–393
Mayer JH, Tomlinson DR, McLean WG (1984) Slow orthograde axonal transport of radiolabeled protein in sciatic motoneurones of rats with short-term experience diabetes: effects of treatment with an aldose reductase inhibitor or myo-inositol. J Neurochem 43:1265–1270
Prineas JB (1969) The pathogenesis of dying-back polyneuropathies. II. An ultrastructural study of experimental acrylamide intoxication in the cat. J Neuropathol Exp Neurol 28:598–621
Sahenk Z, Mendell JR (1979) Ultrastructural body of zinc pyridinethione-induced peripheral neuropathy. J Neuropathol Exp Neurol 38:532–550
Schaumburg HH, Spencer PS (1976) Central and peripheral nervous system degeneration produced by pure n-hexane. An experimental study. Brain 99:183–192
Schaumburg HH, Wisniewski H, Spencer PS (1974) Ultrastructural studies of the dying-back process. 1. Peripheral nerve terminal and axon degeneration in systemic acrylamide intoxication. J Neuropathol Exp Neurol 33:260–284
Schmidt RE, Scharp DW (1982) Axonal dystrophy in experimental diabetic neuropathy. Diabetes 31:761–770
Schmidt RE, Plurad SB, Modert CW (1983) Experimental diabetic autonomic neuropathy characterization in streptozotocin-diabetic Sprague-Dawley rats. Lab Invest 49:538–552
Seppäläinen AM, Haltia M (1980) Carbon disulphide. In Spencer PS, Schaumburg EE (eds) Experimental and clinical neurotoxicology. Williams & Wilkins, Baltimore, pp 356–373
Sharma AK, Thomas PK (1975) Peripheral nerve regeneration in experimental diabetes. J Neurol Sci 24:417–424
Sharma AK, Thomas PK, DeMolina AF (1977) Peripheral nerve fiber size in experimental diabetes. Diabetes 26:689–692
Sharma AK, Bajada S, Thomas PK (1981) Influence of streptozotocin-induced diabetes on myelinated nerve fibre maturation and on body growth in the rat. Acta Neuropathol (Berl) 53:257–265
Sidenius P (1982) The axonopathy of diabetic neuropathy. Diabetes 31:356–363
Sima AAF (1980) Peripheral neuropathy in the spontaneously diabetic BB Wistar rat. An ultrastructural study. Acta Neuropathol (Berl) 51:223–227
Sima AAF (1985) Can the BB rat help to unravel diabetic neuropathy? Neuropathol Appl Neurobiol 11:253–264
Sima AAF, Brismar T (1985) Reversible diabetic nerve dysfunction: structural correlates to electrohysiological abnormalties. Ann Neurol 18:21–29
Sima AAF, Lorusso AC, Thiebert P (1982) Distal symetric polyneuropathy in the spontaneously diabetic BB Wistar rat. An ultrastructural and teased fiber study. Acta Neuropathol (Berl) 58:39–47
Spencer PS, Schaumburg HH (1974) A review of acrylamide neurotoxicity and pathologic mechanisms. Can J Neurol Sci 1:152–168
Spencer PS, Schaumburg HH (1975) Experimental neuropathy produced by 2.5-hexanedione. A major metabolite of the neurotoxic industrial solvent methyl n-butyl ketone. J Neurol Neurosurg Psychiatry 38:771–775
Spencer PS, Schaumburg HH (1976) Central and peripheral distal axonopathy. The pathology of dying-back polyneuropathies. Prog Neuropathol 3:253–295
Spencer PS, Schaumburg HH (1977) Ultrastructural studies of the dying-back process. III. The evolution of experimental peripheral giant axonal degeneration. J Neuropathol Exp Neurol 36:276–299
Spencer PS, Schaumburg HH (1977) Ultrastructural studies of the dying-back process. IV. Differential vulnerability of PNS and CNS fibres in experimental central-peripheral distal axonopathies. J Neuropathol Exp Neurol 36:300–320
Spencer PS, Schaumburg HH, Releigh RL, Tehaar CJ (1975) Nervous system degeneration produced by the individual solvent methyl n-butyl ketone. Arch Neurol 32:219–222
Sugimura K, Windebank AJ, Natarajan V, Lambert EH, Schmid HHO, Dyck PJ (1980) Interstitial hyperosmolarity may cause axis cylinder shrinkage in streptozotocin diabetic nerve. J Neuropathol Exp Neurol 39:710–721
Suzuki K, Pfaff LD (1973) Acrylamide neuropathy in rats. Acta Neuropathol (Berl) 24:197–213
Szendzikowski S, Stetkiewicz J, Wroňska-Noffer T, Karasek M (1973) Structural aspects of the experimental carbon disulphide neuropathy. I. Development of neurohistological changes in chronically intoxicated rats. Int Arch Arbeitsmed 31:135–149
Szendzikowski S, Stetkiewicz J, Wroňska-Noffer T, Karasek M (1974) Pathomorphology of the experimental lesion of the peripheral nervous system in white rats chronically exposed to carbon disulphide. In: Hausmanowa-Petrusiewicz I, Jedrzejowska H (eds) Structure and function of normal and diseased muscle and peripheral nerve. Polish Medical Publishers, Warsaw, pp 319–326
Thomas PK, Jeffreys JGR, Sharma AK, Bajada SJ (1981) Nerve conduction velocity in experimental diabetes in the rat and rabbit. J Neurol Neurosurg Pysachiatry 44:233–246
Tomlinson DR, Mayer JH (1984) Defects of axonal transport in diabetes mellitus — A possible contribution to the etiology of diabetic neuropathy. J Auton Pharmacol 4:59–72
Vitadello M, Filliatreau G, Dupont JL, Hässig R, Gorio A, Di Giamberardino L (1984) Altered axonal transport of cytoskeletal proteins in the diabetic mouse C57BL/Ks (db/db). J Submicrosc Cytol 16:199
Vuorinen V, Röyttä M, Raine CS (1989) The long-term effects of a single injection of taxol upon peripheral nerve axons. J Neurocytol 18:775–783
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jirmanová, I. Giant axonopathy in streptozotocin diabetes of rats. Acta Neuropathol 86, 42–48 (1993). https://doi.org/10.1007/BF00454897
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00454897