Summary
In sciatic nerves of rats, there are more than twice as much unmyelinated than myelinated axons. Their ratio varies in a wide range from one area to the other. Some regressive changes are seen already in unmyelinated axons of normal controls (loss of structural components, axonal beading). Usually, these alterations can be distinguished from early experimental lesions by the lack of characteristic Schwann cell reactions.
In the beginning of INH-neuropathy, fewer unmyelinated than myelinated nerve fibers are degenerating. Some of the unmyelinated axons may become irregularily folded, swollen, or shrunken while there is a progressive loss of tubules, filaments, normal mitochondria, and sometimes an increase in the thickness of the axolemma.
The axonal changes are accompanied by a disturbance of the normal axon-Schwann cell relation. Initially, some Schwann cells may become extremely irregular; later they lose their surface differentiation while their cross sectional contour becomes rather rounded.
In general, unmyelinated axons in INH-neuropathy show similar alterations and disturbances of the axon-Schwann cell relation as seen in Wallerian degeneration. Yet extremely deformed unmyelinated nerve fibers, axons as well as Schwann cells, and mitochondrial granules were only observed in INH-neuropathy.
Zusammenfassung
Im N. ischiadicus der Ratte kommen etwa doppelt so viele marklose als markhaltige Nervenfasern vor. Das normale zahlenmäßige Verhältnis dieser beiden Fasertypen schwankt in weiten Grenzen. Schon im ungeschädigten Nerven lassen sich bereits an einzelnen marklosen Nervenfasern verschiedenartige regressive Veränderungen wie Strukturverlust und perlschnurförmige Auftreibungen nachweisen; sie sind in der Regel von akuten, toxisch bedingten Veränderungen durch das Fehlen charakteristischer Schwann-Zellreaktionen zu differenzieren.
Bei der INH-Neuropathie degenerieren anfangs im Verhältnis zu den markhaltigen nur wenige marklose Nervenfasern. Einige marklose Axone können unregelmäßig konturiert, geschwollen oder geschrumpft erscheinen; dabei lösen sich die Tubuli und Filamente auf; in manchen Fällen verdichtet sich ausch das Axolemm.
Die Axonveränderungen werden von Störungen der normalen Axon-Schwann-Zellrelation begleitet. In den Anfangsstadien können manche Schwann-Zellen hochgradig deformiert sein; später verlieren sie ihre Oberflächendifferenzierung und runden sich (auf dem Querschnitt) ab.
In der Regel zeigen die marklosen Nervenfasern bei der INH-Neuropathie die gleichen Veränderungen und Störungen der Axon-Schwann-Zellrelation wie bei der Wallerschen Degeneration. Extreme prolapsartige Verformungen von Axonen und Schwann-Zellen sowie mitochondriale Granula haben wir jedoch nur bei der INH-Neuropathie, nicht aber bei der Wallerschen Degeneration beobachtet.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Literatur
Bartmann, K., Coper, H., Jütte, R.: Die NAD(P)-Glykohydrolase in Tuberkulosebacterien. Ein Beitrag zum Wirkungsmechanismus des INH. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.257, 8 (Abstract) (1967).
Bischoff, A.: The ultrastructure of tri-ortho-cresyl-phosphat-poisoning. I. Studies on myelin and axonal alterations in the sciatic nerve. Acta neuropath. (Berl.)9, 158–174 (1967).
Blümcke, S.: Zur Morphologie und Genese des Leitgewebes peripherer Nervenfaserregenerate. II. Elektronenmikroskopische Befunde aus der Nervennarbe. Zbl. allg. path. Anat.104, 241–255 (1963).
—: Elektronenoptische Untersuchungen an Schwannschen Zellen während der initialen Degeneration und frühen Regeneration. Beitr. path. Anat.128, 238–258 (1963).
—, Niedorf, H. R.: Electron microscope studies of Schwann cells during the Wallerian degeneration with special reference to the cytoplasmic filaments. Acta neuropath. (Berl.)6, 46–60 (1966).
——, Rode, J.: Axoplasmic alterations in the proximal and distal stumps of transsected nerves. Acta neuropath. (Berl.)7, 44–61 (1966).
—, Themann, H., Niedorf, H. R.: The deposition of glycogen during the degeneration and regeneration in sciatic nerves of rabbits. Light and electron microscopic studies. Acta neuropath. (Berl.)5, 69–81 (1965).
Brock, N., Wilk, W.: Zur Ernährung der Laboratoriumstiere. Arzneimittel-Forsch. (Drug. Res.)11, 1071–1086 (1961).
Cajal, S. R.: Studien über Nervenregeneration. Leipzig: Joh. Ambr. Barth 1908.
Castro, F. de: Recherches sur la dégénération et la regénération du système nerveux sympatique. Quelques observations sur la constitution des synapses dans les ganglions. Trab. Lab. invest. Biol.26, 357–456 (1930).
Cavanagh, J. B.: On the pattern of changes in peripheral nerves produced by isoniazid intoxication in rats. J. Neurol. Neurosurg. Psychiat.30, 26–33 (1967).
Danilova, L. V.: An increasing contrast of cell membranes in allantoic epithelium under degenerative variations. In: Electron Microscopy 1966, Volume II, ed. by R. Uyeda. Tokyo: Maruzen 1966.
Descarries, L., Schröder, J. M.: Fixation du tissu nerveux par perfusion a grand débit. J. Microscopie7, 281–286 (1968).
Echandia, E. L. R., Piezzi, R. S.: Microtubules in the nerve fibers of the toad Bufo Arenarum Hensel. J. Cell Biol.39, 491–497 (1968).
Elfvin, L. G.: The ultrastructure of unmyelinated fibers in the splenic nerve of the cat. J. Ultrastruct.1, 428–454 (1958).
—: Electron microscopic investigation of the plasma membrane and myelin sheath of autonomic nerve fibers in the cat. J. Ultrastruct. Res.5, 388–407 (1961).
Engström, H., Wersäll, J.: Myelin sheath structure in nerve fibre demyelinisation and branching regions. Exp. Cell Res.14, 414–425 (1958).
Estable-Puig, J. F., Bauer, W. C., Blumberg, J. M.: Paraphenylenediamine staining of osmium-fixed plastic embedded tissue for light and phase microscopy. J. Neuropath. exp. Neurol.24, 531–535 (1965).
Gamble, H. J.: Comparative electron microscopic observations on the connective tissues of a peripheral nerve and a spinal nerve root in the rat. J. Anat. (Lond.)98, 17–25 (1964).
—, Gosset, J. M.: Specialization of Schwann cell membranes. Nature (Lond.)212, 734–735 (1966).
Gangadharam, P. R. J., Harold, F. M., Schaefer, W. B.: Selective inhibition of nucleic acid synthesis in mycobacterium tuberculosis by isoniazid. Nature (Lond.)198, 712–714 (1963).
Gasser, H. S.: Properties of dorsal root unmyelinated fibers on the two sides of the ganglion. J. gen. Physiol.38, 709–728 (1955).
Glimstedt, G., Wohlfahrt, G.: Electron microscopic observations on Wallerian degeneration in peripheral nerves. Acta morph. neerl.-scand.3, 135–146 (1960).
——: Electron microscopic studies on peripheral nerve regeneration. Lunds universitets arsskrift16, 1–22 (1960).
Greenawalt, J. W., Rossi, C. S., Lehninger, A. L.: Effect of active accumulation of calcium and phosphate ions on the structure of rat liver mitochondria. J. Cell Biol.23, 21–38 (1964).
Honjin, R., Nakamura, T., Imura, M.: Electron microscopy of peripheral nerve fibers. III. On the axoplasmic changes during Wallerian degeneration. Okajimas Folia anat. jap.33, 131–156 (1959).
Karnovsky, M. J.: The fine structure of mitochondria in the frog nephron, correlated with cytochrome oxidase activity. Exp. molec. Path.2, 347–366 (1963).
Klinghardt, G. W.: Experimentelle Nervenfaserschädigungen durch Isonicotinsäurehydrazid und ihre Bedeutung für die Klinik. Verh. dtsch. Ges. inn. Med. (Kongr.)60, 764–768 (1954).
Klinghardt, G. W.: Arzneimittelschädigungen des peripheren Nervensystems unter besonderer Berücksichtigung der Polyneuropathie durch Isonicotinsäurehydrazid (experimentelle und human-pathologische Untersuchungen). Proc. Vth Internat. Congr. Neuropath. Sept. 1965, S. 292–301.
Krulik, R.: Der Einfluß von Hydrazin und Isonicotinsäurehydrazid auf bestimmte Substanzen des Zuckerstoffwechsels in vitro. Arzneimittel-Forsch.16, 1623–1626 (1966).
Levene, C. I.: The lathyrogenic effect of isonicotinic acid hydrazide (INAH) on the chick embryo and its reversal by pyridoxal. J. exp. Med.113, 795–811 (1961).
Nathaniel, E. J. H., Pease, D. C.: Degenerative changes in rat dorsal roots during Wallerian degeneration. J. Ultrastruct. Res.9, 511–532 (1963).
——: Regenerative changes in rat dorsal roots following Wallerian degeneration. J. Ultrastruct. Res.9, 533–549 (1963).
——: Collagen and basement membrane formation by Schwann cells during nerve regeneration. J. Ultrastruct. Res.9, 550–560 (1963).
Ochoa, J., Mair, W. G. P.: The normal sural nerve in man. I. Ultrastructure and numbers of fibres and cells. Acta neuropath. (Berl.)13, 197–216 (1969).
—: Behaviour of peripheral nerve structures in chronic neuropathies, with special reference to the Schwann cell. J. Anat. (Lond.)102, 95–111 (1967).
Pasquali-Ronchetti, J., Greenawalt, Carafoli, E.: On the nature of the dense matrix granules of normal mitochondria. J. Cell Biol.40, 565–568 (1969).
Ohmi, S.: Electron microscopic study on Wallerian degeneration of the peripheral nerve. Z. Zellforsch.54, 39–67 (1961).
Peachy, C. D.: Electron microscopic observations on the accumulation of divalent cations in intramitochondrial granules. J. Cell Biol.20, 95–111 (1964).
Poche, R.: Elektronenmikroskopische Untersuchungen zur Morphologie des Herzmuskels vom Siebenschläfer während des aktiven und lethargischen Zustandes. Z. Zellforsch.50, 332–360 (1959).
Ranson, S. W.: Degeneration and regeneration of nerve fibers. J. comp. Neurol.22, 487–547 (1912).
Schaefer, W. R.: Effect of isoniazid on the dehydrogenase activity of mycobacterium tuberculosis. J. Bact.79, 236–245 (1960).
Schlaepfer, W. W., Hager, H.: Ultrastructural studies of INH-induced neuropathy in rats. I. Early axonal changes. Amer. J. Path.45, 209–220 (1964).
——: Ultrastructural studies in INH-induced neuropathy in rats. II. Alteration and composition of myelin sheath. Amer. J. Path.45, 423–433 (1964).
——: Ultrastructural studies in INH-induced neuropathy in rats. III. Repair and regeneration. Amer. J. Path.45, 679–689 (1964).
Schröder, J. M.: Die Hyperneurotisation Büngnerscher Bänder bei der experimentellen Isoniazid-Neuropathie: Phasenkontrast- und elektronenmikroskopische Untersuchungen. Virchows Arch., Abt. B Zellpath.1, 131–156 (1968).
Taxi, J. T.: Etude au microscope electronique de la dégénérescence Wallérienne des fibres nerveuse amyeliniques. C. R. Acad. Sci. (Paris)248, 2796–2798 (1959).
Terry, R. D., Harkin, J. C.: Wallerian degeneration and regeneration of peripheral nerves. In Biology of Myelin, p. 303. Ed. by S. A. Korey. New York: P. B. Hoeber 1959.
Thomas, R. S., Greenawalt, J. W.: Microincineration, electron microscopy, and electron diffraction of calcium phosphate-loaded mitochondria. J. Cell Biol.39, 55–76 (1968).
Tomcsanyi, A.: Effect of isoniazid on the incorporation of amino acids into protein by a soluble system of mycobacteria. Amer. Rev. resp. Dis.92, 119–120 (1965).
Venable, J. H., Coggeshall, R.: A simplified lead citrate stain for use in electron microscopy. J. Cell Biol.25, 407–408 (1965).
Vial, J. D.: The early changes in axoplasm during Wallerian degeneration. J. biophys. biochem. Cytol.4, 551–556 (198).
Webster, H. deF.: Transient focal accumulations of axonal mitochondria during the early stages of Wallerian degeneration. J. Cell Biol.12, 361–383 (1962).
—, Collins, G. H.: Comparison of osmium tetroxide and glutaraldehyde perfusion fixation for the electron microscopic study of the normal rat peripheral nerve. J. Neuropath. exp. Neurol.23, 109–126 (1964).
Wechsler, W., Hager, H.: Elektronenmikroskopische Untersuchung der sekundären Wallerschen Degeneration des peripheren Säugetiernerven. Beitr. path. Anat.126, 352–380 (1962).
Weiss, J. M.: Mitochodrial changes induced by potassium and sodium in the duodenal absorptive cell as studied with the electron microscope. J. exp. Med.102, 783–788 (1955).
Yates, R. D., Yates, J. C.: The occurence of intramitochondrial granules in nerve cells. Z. Zellforsch.92, 388–393 (1968).
Yoneda, M., Kato, N., Okajama, M.: Competitive action of isonicotinic acid hydrazide and vitamin B6 in formation of indole by E. coli. Nature (Lond.)170, 803 (1952).
Zbinden, G., Studer, A.: Experimenteller Beitrag zur Frage der Isoniazid-Neuritis und ihre Beeinflussung durch Pyridoxin. Z. Tuberk.107, 97–107 (1955).
Zelená, J., Lubińska, L., Gutmann, E.: Accumulation of organelles at the ends of interrupted axons. Z. Zellforsch.91, 200–219 (1968).
Zeller, E. A., Barsky, J., Touts, J. R., Kirchheimer, W. F., van Orden, L. S.: Influence of isnicotinic acid hydrazide (INH) and 1-isonicotinyl-2-isopropylhydrazide (IIH) on bacterial and mammalian enzymes. Experientia (Basel)8, 349–350 (1952).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schröder, J.M. Die Feinstruktur markloser (Remakscher) Nervenfasern bei der Isoniazid-Neuropathie. Acta Neuropathol 15, 156–175 (1970). https://doi.org/10.1007/BF00685268
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00685268