Summary
Application of a longitudinal current to fresh unfixed nerves produced, in 2 hrs, various types of axon swellings which were indistinguishable from reactive axon swellings in pathological material. Production of these swellings depended on an adequate time of exposure, an adequate current, and a local injury to the fiber.
In electrophoretically produced axon swellings, many oxidative enzymes accumulated such as: DPN-diaphorase, TPN-diaphorase, cytochrome oxidase, succinic dehydrogenase, lactic dehydrogenase, isocitric dehydrogenase, malic dehydrogenase, glutamate dehydrogenase, and alcohol dehydrogenase. Alkaline and acid phosphatase did not accumulate in axonal swellings. There was also an accumulation of mitochondria, lipids (probably in mitochondrial membranes), proteins, carbohydrates, and ribonucleic acid. This array of substances was identical with that found in reactive axonal swellings produced both experimentally and pathologically in vivo.
Axoplasm in reactive axon swellings that were produced in vivo showed the same electrophoretic convection as axoplasm of normal fibers.
Accumulation of substances in an axon swelling can result from a confined local shift of axoplasm; it does not inherently indicate a changed rate of production by the nerve cell.
Physiological currents in the tissue may well be responsible for the development of “reactive” axon swellings, as well as for the normal convection of axoplasm.
Zusammenfassung
Die Anwendung von Längsdurchströmung auf frische, unfixierte Nerven erzeugt nach 2 Std verschiedene Arten von Axonschwellungen, welche von reaktiven Axonschwellungen in pathologischem Material nicht unterscheidbar sind. Die Erzeugung dieser Schwellungen hängt von der adäquaten Zeit des Stromdurchflusses, von adäquaten Stromkonstanten und von der lokalen Schädigung der Faser ab.
In den elektrophoretisch erzeugten Axonschwellungen häufen sich viele oxydative Enzyme an: so DPN-Diaphorase, TPN-Diaphorase, Cytochrom-Oxydase, Bernsteinsäure-Dehydrogenase, Milchsäure-Dehydrogenase, Isocitronensäure-Dehydrogenase, Äpfelsäure-Dehydrogenase, Glutamat-Dehydrogenase und Alkohol-Dehydrogenase. Alkalische und saure Phosphatase waren in den Axonschwellungen nicht vermehrt. Ebenso wird eine Anhäufung von Mitochondrien sowie von Lipoiden (wahrscheinlich in Mitochondrienmembranen), Proteinen, Kohlenhydrat und Ribonucleinsäure festgestellt. Diese Gruppierung von Substanzen ist identisch mit jener, die in reaktiven Axonschwellungen sowohl im Experiment als auch unter pathologischen Bedingungen in vivo gefunden wird.
Das Axoplasma von intravital erzeugten Axonschwellungen besitzt die gleiche elektrophoretische Mobilität wie das Axoplasma normaler Nervenfasern.
Die Substanzanhäufung in Axonschwellungen kann von einer lokal begrenzten Axoplasmaströmung herrühren; sie weist nicht unbedingt auf eine geänderte Produktionsrate in der Nervenzelle hin.
Physiologische Ströme im Gewebe können ebenso für die Entstehung von “reaktiven” Axonschwellungen wie für die normale Axoplasmaströmung verantwortlich gemacht werden.
Similar content being viewed by others
References
Becker, R. O., C. H. Bachman andW. H. Slaughter: Longitudinal direct-current gradients of spinal nerves. Nature (Lond.)196, 675–676 (1962).
Bethe, A.: Über die Natur der Polarisationsbilder, welche durch den konstanten Strom am Nerven hervorgerufen werden können. Z. Biol.52, 146–152 (1909).
—: Nervenpolarisationsbilder und Erregunstheorie. Pflügers Arch. ges. Physiol.183, 28 bis 302 (1920).
Ramon y Cajal, S.: Degeneration and regeneration of the nervous system, p. 1928.R. M. May (trans., and ed.). New York: Hafner Publ. Co. 1959.
Droz, B., andC. P. Leblond: Migration of proteins along the axons of the sciatic nerve. Science137, 1047–1048 (1962).
Friede, R. L.: Transport of oxidative enzymes in nerve fibers; a histochemical investigation of the regenerative cycle in neurons. Exp. Neurol.1, 441–466 (1959).
—: Enzyme histochemical studies in multiple sclerosis. Arch. Neurol (Chic.)5, 433–443 (1961).
—: An enzyme histochemical study of cerebral arteriosclerosis; with some data on the pathogenesis of periarterial scars. Acta neuropath. (Berl.)2, 58–72 (1962).
—,L. M. Fleming andM. Knoller: A quantitative appraisal of enzyme histochemical methods in brain tissue. J. Histochem. Cytochem.11, 232–245 (1963).
Gerard, R. W.: Nerve metabolism. Physiol. Rev.12, 469–592 (1932).
Hebb, C., andA. Silver: Gradient of cholinesterase activity and of choline acetylase activity in nerve fibers; gradient of choline acetylase activity. Nature (Lond.)189, 123–125 (1961).
—, andG. Walthes: Choline acetylase in antero- and retro-grade degeneration of a cholinergic nerve. J. Physiol. (Lond.)132, 667–671 (1956).
Heinzen, B.: Acid phosphatase activity in transected sciatic nerve. Anat. Rec.98, 193–207 (1949).
Hodler, J., R. Stämpfli andI. Tasaki: Role of potential wave spreading along myelinated nerve fiber in excitation and conduction. Amer. J. Physiol.170, 375–389 (1952).
Huxley, A. F., andR. Stämpfli: Evidence for saltatory conduction in peripheral myelinated nerve fibers. J. Physiol. (Lond.)108, 315–339 (1949).
——: Saltatory transmission of the nervous impulse. Arch. Sci. Physiol.3, 435–447 (1949).
Katsura, S.: Über Wirkungen des konstanten Stroms auf das mikroskopische Bild des Nerven. Pflügers Arch. ges. Physiol.217, 279–292 (1927).
Koenig, H.: The synthesis and peripheral flow of axoplasm. Trans. Amer. Neurol. Ass.83, 162–164 (1928).
Koenig, E., andG. B. Koelle: Mode of regeneration of acetylcholinesterase in cholinergic neurons following irreversible inactivation. J. Neurochem.8, 169–188 (1961).
Lajtha, A.: Protein metabolism in nerve. In: Chemical pathology of the nervous system (J. Folch-Pr, ed.), p. 268–276. Pergamon Press 1961.
Lewis, P. R., andA. F. W. Hughes: The cholinesterase of developing neurones in Xenopus laevis, p. 511–514. In: Metabolism of the nervous system (Derek Richter ed.), p. 511–514. Pergamon Press 1957.
Lubińska, L., S. Niemierko andB. Oderfeld: Gradient of cholinesterase activity and of choline acetylase activity in nerve fibers; gradient of cholinesterase activity. Nature (Lond.)189, 123–125 (1961).
———, andL. Szwark: Decrease of acetylcholinesterase activity along peripheral nerves. Science135, 368–370 (1962).
Marchart, J.: Alkaline phosphatase activity in normal and degenerating peripheral nerves of the rabbit. J. Anat. (Lond.)83, 229–237 (1949).
Miani, N.: Evidence of proximo-distal movement along the axon of phospholipid synthetized in the nerve cell body. Nature (Lond.)193, 887–888 (1962).
Novelli, A.: A short method for chondriome. J. Histochem. Cytochem.10, 102–103 (1962).
Ochs, S., andE. Burger: Movement of substance proximo-distally in nerve axons as studied with spinal cord injections of radioactive phosphorus. Amer. J. Physiol.194, 499–506 (1958).
— andG. Richards: Axoplasmic flow in ventral root nerve fibers of the cat. Exp. Neurol.5, 349–363 (1962).
— andW. E. DeMyer: Axoplasmic flow rates during nerve regeneration. Exp. Neurol.2, 627–637 (1960).
Pearse, A. G. E.: Histochemistry: Theoretical and applied. Second Ed. Boston: Little, Brown, and Co. 1961.
Roeder, F.: Über Elektrolytegehalt und elementare Zusammensetzung des Froschnerven in dem Verlauf der Leitungsstrecke und ihre Veränderungen mit der Reizung. Biochem. Z.227, 715–726 (1931).
Samuels, A. J., L. L. Boyarsky, R. W. Gerard, B. Libet andM. Brunt: Distribution exchange and migration of phosphate compounds in the nervous system. Amer. J. Physiol.164, 1–15 (1951).
Sato, K.: On the influence of electric polarization upon the stainability of nerve. Folia anat. jap.7, 33–43 (1929).
Sawyer, C. H.: Cholinesterases in degenerating and regenerating peripheral nerves. Amer. J. Physiol.146, 246–253 (1946).
Schlote, W.: Morphologische und histochemische Untersuchungen an retrograden Axonveränderungen im Zentralnervensystem. Acta neuropath. (Berl.)1, 135–158 (1961).
Schwartz, A.: Über die Beeinflussung der primären Färbbarkeit und der Leitungsfähigkeit des polarisierten Nerven durch die den Strom zuführenden Ionen. Pflügers Arch. ges. Physiol.138, 487–524 (1911).
Seeman, J.: Über die Bedeutung der Färbbarkeitsänderung tierischer Gewebe durch elektrische Polarisation. Z. Biol.53, 287–302 (1909).
Snell, R. S.: Changes in the histochemical appearances of cholinesterase in a mixed peripheral nerve following nerve section and compression injury. Brit. J. exp. Path.38, 479–482 (1957).
Waelsch, H.: Some aspects of amino acid and protein metabolism of the nervous system. J. nerv. ment. Dis.126, 33–39 (1958).
Weiss, P.: Endoneurial edema in constricted nerve. Anat. Rec.86, 491–522 (1943).
—: Damming of axoplasm in constricted nerve: A sign of perpetual growth in nerve fibers. Anat. Rec.88, 464–465 (1944).
—: Evidence of perpetual proximo-distal growth of nerve fibers. Biol. Bull.87, 160 (1944).
Weiss, P.: The concept of perpetual neuronal growth and proximodistal-substance convection. In: Regional Neurochemistry (S. S. Kety andJ. Elkes, ed.), p. 220–242. Pergamon Press 1961.
—, andH. B. Hiscoe: Experiments on the mechanism of nerve growth. J. exp. Zool.107, 315–395 (1948).
—,C. Taylor andP. Pillai: The nerve fiber as a system in continuous flow: Microcinematographic and electromicroscopic demonstrations. Science136, 330 (1962).
—H. Wang, A. C. Taylor andM. V. Edds jr.: Proximo-distal fluid convection in the endoneurial spaces of peripheral nerves, demonstrated by colored and radioactive (isotope) tracers. Amer. J. Physiol.143, 521–540 (1945).
Young, J. Z.: Contraction, turgor, and the cytoskeleton of nerve fibers. Nature (Lond.)153, 333–335 (1944).
Yuien, K., andK. Sato: On the spreading path of stains injected into the nerve. Folia anat. Jap.7, 419–423 (1929).
Zelená, J., andL. Lubińska: Early changes of acetylcholinesterase activity near the lesion in crushed nerves. Physiol. bohemoslov.11, 261–268 (1962).
Author information
Authors and Affiliations
Additional information
With 5 Figures in the Text
This investigation was supported by U.S. Public Health Service, Grant No. B-3250.
Rights and permissions
About this article
Cite this article
Friede, R.L. Electrophoretic production of “reactive” axon swellings in vitro and their histochemical properties. Acta Neuropathol 3, 217–228 (1964). https://doi.org/10.1007/BF00684397
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00684397