from the nerve-fibres the cells of the connective tissue in the neighbourhood of the fibres become charged with fatty granules, which may have become formed from the dissolved fatty substances of the medullary sheath.

These degenerative changes seem to occur simultaneously along the whole length of the nerve. In the nerves to voluntary muscles the end-plate is said to be the part first affected.

In the immediate neighbourhood of the section the appearances are somewhat modified by the escape of the myelin from the cut ends of the nerve-fibre, and the infiltration of blood and lymph into the interior of the ends thus emptied of their contents. This change must of course occur both in the central stump of the nerve as well as in the peripheral cut end: it does not often extend beyond the first node. Apart from such traumatic modification, true degenerative changes do not occur in the end of the nerve which is still in connection with the centre, although proliferation of the nucleus in the first and second internodes near the cut may take place. The central cut end of the axis-cylinder does not become altered; except that it undergoes a slight swelling, preparatory in all probability to the renewed growth by which the regeneration of the fibre is effected.

Regeneration proceeds but slowly. Up to the twenty-eighth day after the section, or even later than this, there is still no trace of the new nerve-fibres in the peripheral part of the nerve. With the exception of a few fibres which for some reason not well understood (probably because they are derived from some other nerve which has not been cut, and are taking a recurrent course in the cut nerve), have not undergone degeneration, nothing is to be seen in a section of the nerve at this period, except the primitive sheaths of the old fibres, filled with clear or finely granular substance. If, however, a transverse section be made of a nerve considerably later than this (sixty or seventy days after the original section) it is found that within the tubes formed by the old primitive sheaths, according to Vanlair between them, small single fibres or groups of fibres, either pale or provided with a medullary sheath, are to be seen, besides here and there those drops of myelin which have remained unabsorbed from the medullary sheaths of the original fibres. On cutting out the central end of the nerve, together with the cicatrix, and separating its fibres, it is seen that the groups of small fibres noticed in the transverse section are continuous with the central ends of the axis-cylinders of the original nerve (fig. 416, D). Either a bunch of small fibres may grow directly from the axis-cylinder of one fibre, or two only may emerge from this; but these soon bifurcate, and, repeating this process again and again, may eventually form a considerable group. It would appear therefore that the regeneration of a cut nerve is effected by a growth of new fibres from the axis-cylinders of the central cut end, and that many more such fibres are formed in the first instance than the old ones which have undergone degeneration. The growth from the old axis-cylinders always occurs in the situation of a node -either the one nearest to the section or one somewhat higher up. The new fibres are at first pale but subsequently acquire a medullary sheath, still later a primitive sheath, with constrictions of Ranvier, which, as in young nerves, are placed at much more frequent intervals than in the old fibres, so that the intervals are much shorter.

The fibres which grow thus in groups from the old axis-cylinders are often very irregular in their course, twisting around one another, and even looping back in some places for a considerable distance. In the cicatrix especially is this irregularity and obliquity of disposition noticeable, probably on account of the absence here of the guide formed by the sheaths of the original fibres.

Restoration of function in the nerve may not occur for several months, during which time it may be presumed the new nerve-fibres are slowly finding their way

along the course of those which have been destroyed as a result of the section. Of the numerous fibres in the groups above described, no doubt a few only eventually assume the function of the fibres which they replace, but the later steps of the process of regeneration have not yet been fully followed out.

Except close to the actual place of section, where they are somewhat hypertrophied, the connective-tissue sheaths of the nerves remain unaltered. In the cicatrix the new nerve-fibres do not at first run in definite sheaths, but these become subsequently developed from the connective-tissue around, so that at length the restoration of continuity of all the structures in the nerve becomes complete. Vanlair states that the outbudding of the axis-cylinders of the central end may occur as much as one or two centimeters from the point of section, and may involve at first only the peripheral fibres of a funiculus.

Ranvier looks upon the regeneration of a nerve by growth from the intact central ends of the fibres as illustrating the tendency which, he believes, all nerve-fibres. exhibit, to grow continuously until a hindrance is met with, and he compares the result of cutting a nerve-fibre in causing the growth of a number of new fibres in place of the original one, to that produced when the leading shoot of a plant is removed, in causing the production of a number of lateral buds.

Some have thought that under favourable circumstances an immediate union between the ends of the nerve-fibres may happen after section; but considering the impossibility of procuring exact apposition of the individual fibres, end to end, as well as the inevitable extension of the effects of the mechanical injury caused by the section along the soft contents of the primitive sheath, it seems improbable that such direct union should ever occur.

The degeneration does not affect, as we have seen, the part of the nerve remaining in connection with the nervous centre, which seems to exert an influence in maintaining the nutrition of the nerve. The ganglia, as well as the grey matter of the brain and spinal cord, are centres of this influence. It is found that, in the central portion of a divided spinal nerve, while the fibres belonging to the anterior root owe their integrity to their connection with the spinal cord (and especially with the large cells of the anterior cornu), those of the posterior root are similarly dependent on the ganglion; and that if the posterior root be cut between the ganglion and the spinal cord, not only will the fibres which pass from it into the trunk of the nerve beyond the ganglion remain unchanged, but also those above the ganglion, in the portion of the root left in connection with it; whereas the fibres of the same root which remain connected with the cord but severed from the ganglion degenerate.

The degeneration of the peripheral end of a cut nerve and the breaking up of the substance of the medullary sheath were first noticed by Nasse in 1839. But the discovery by Augustus Waller in 1852 of the dependence of the process upon isolation of the nerve-fibre from its nutritive centre, and his application of this discovery to the tracing the course of nerve-fibres in peripheral parts (now known as the Wallerian method) first gave full interest and importance to the observation of Nasse. Stated briefly, the law may be formulated as follows:"Degeneration occurs along the whole extent of any nerve-fibre which is cut off from the cell which governs its nutrition," and this, as the observations of His have shown, is in every case the cell from which the nerve-fibre has originally grown.'

RECENT LITERATURE

Arnold, Julius, Bemerkungen über Spiralfasern und pericelluläre Fadennetze an den Ganglienzellen des Sympathicus, Anatomischer Anzeiger, 1890.

Aronson, H., Beiträge zur Kenntniss der centralen und peripheren Nervenendigungen, Dissert., Berlin, 1886.

Boveri, Th., Beiträge zur Kenntniss der Nervenfasern, Abhandl. d. k. bayerisch. Akad. d. Wissenschaften zu München, 1885.

1 The addendum which is sometimes made to the effect that the course of the degeneration follows that of the nervous impulses which are ordinarily conducted along the fibre is manifestly erroneous.

Brand, The nerve terminations in the cornea, Archives of Ophthalmology, 1889. Burckhardt, K. R., Histologische Untersuchungen am Rückenmark der Tritonen, Arch. f. mikrosk. Anat., Bd. xxxiv., 1889.

Capobianco, F., e Germano, E., Contribuzione alla istologia delle fibre nervose midollate. Giornale della Associaz. dei Naturalisti e Med. di Napoli, 1890.

Cattaneo, A., Organes nerveux terminaux musculo-tendineux, leurs conditions normales et leur manière de se comporter après la section des racines nerveuses et des nerfs spinaux, Archives ital. de biologie, 1888.

Cattani, Giuseppina, Sulla degenerazione e neoformazione delle fibre nervose-midollari periferiche, Archivio per le scienze mediche, vol. xi., 1887; L'appareil de soutien de la myéline dans les fibres nerveuses périphériques, Archives italiennes de biologie, t. vii., 1886.

Ciaccio, G. V., Note sur la terminaison des fibres nerveuses, Archives italiennes de biologie, iii.; Osservazioni istologiche interno alla terminazione della fibre nervose motive ne' muscoli striati delle torpedini, del topo casalingo e del ratto albino, Memoire dell' accad. di Bologna, 1883; Sur les plaques nerveuses finales dan les tendons des vertébrés, Journal de micrographie, and Archives italiennes de biologie, 1890.

Cuccati, G., Delle terminazione nervose nei muscoli addominali della rana temporaria e della rana esculenta, Internat. Monatssch. f. Anat. u. Hist., Bd. v., 1888.

Daae, H., Zur Kenntniss der Spinalganglienzellen beim Säugethier, Arch. f. mikrosk. Anatomie, Bd. xxxi., 1888.

Erhlich, P., Ueber die Methylenblaureaction der lebenden Nervensubstanz, Deutsche med. Wochenschr., No. 4, und Biologisches Centralb., No. 7, 1886.

Exner, S., Notiz zu der Frage von der Fasernvertheilung mehrerer Nerven in einem Muskel, Pflüger's Archiv, Bd. 36, 1885.

Fajersztajn, J., Recherches sur les terminaisons des nerfs dans les disques terminaux chez la grenouille, Archives de zoologie expérimentale, tome vii., 1889.

Flechsig, Paul, Über eine neue Färbungsmethode des centralen Nervensystems und deren Ergebnisse bezüglich des Zusammenhanges von Ganglienzellen und Nervenfasern, Berichte der königl. Sachs. Gesellschaft, 1889 und 1890.

Flesch, M., Zur Kenntniss der Nervenendigung in den quergestreiften Muskeln des Menschen, Mittheil. d. naturforsch. Gesellsch. in Bern, 1884; Structur der Nervenzellen in peripheren Ganglien, Tagebl. d. Naturforscherversammlung in Strassburg, 1885; Ueber die Verschiedenheiten im chemischen Verhalten der Nervenzellen, Mittheil. d. Naturf. Gessellsch. in Bern, 1887.

Flesch, M., und Koneff, H., Bemerkungen über die Structur der Ganglienzellen, Neurolog. Centralb., 1886.

Fritsch, G., Ueber einige bemerkenswerthe Elemente des Centralnervensystems von Lophius piscatorius, Archiv f. mikrosk. Anat., Bd. xxvii., 1886.

Frommann, Ueber einige Structurverhältnisse der Nervenfasern und Nervenzellen, Zeitschr. f. Psych., Bd. xlvi., 1889.

Fusari e Panasci, S. terminazione nervose n. mucosa e n. ghiandole sierose d. lingua d. mammiferi, Atti d. r. acc. d. scienze di Torino, xxv., 1890.

Gad, J., und Heymans, T. F., Über das Myelin, die myelinhaltigen und myelinlosen Nervenfasern, Archiv f. Anat. u. Physiol., Physiol. Abth., 1890.

Gad, J., u. M. Joseph, Ueber die Beziehungen der Nervenfasern zu der Nervenzellen in den Spinalganglien, Arch. f. Anat. u. Phys., Physiol. Abth., 1889.

Gaskell, W. H., On the relationship between the structure and the function of the nerves which innervate the visceral and vascular systems, Journal of Physiology, vol. vii.

Gedoelst, L., Etude sur la constitution cellulaire de la fibre nerveuse, La Cellule, t. iii., 1887; Nouvelles recherches sur la constitution cellulaire de la fibre nerveuse, La Cellule, t. v. 1889.

Gessler, H., Untersuchungen über die letzten Endigungen der motorischen Nerven im quergestreiften Muskel und ihr Verhalten nach der Durchschneidung der Nervenstämme, Deutsches Archiv f. klinische Medicin, Bd. 33, 1883.

Gierke, H., Die Stützsubstanz des centralen Nervensystems, Neurolog. Centralbl., 1883; Arch. f. mikr. Anat., 1885.

Golgi, C., Recherches sur l'histologie des centres nerveux, Archives italiennes de biologie, t. iii., 1883; Über den feineren Bau des Rückenmarkes, Anatomischer Anzeiger, 1890.

Grünhagen, A., Ueber ein Endothelialelement der Nervenprimitivscheide, Arch. f. mikr. Anat., Bd. xxiii., 1884.

Hanken, J. H., Ueber die Folgen von Quetschung peripherischer Nerven, Internat. Monatsschr. f. Anat. u. Histol., Bd. iii., 1886.

Hartenstein, J., Die topographische Verbreitung der Vater'schen Körperchen beim Menschen, Dissert., Dorpat, 1889.

Haycraft, J. B., Termination of nerves in the nuclei of epithelial cells of tortoise-shel, Quarterly Journal of Micr. Science, xxi., 1890.

Haycraft, J. B., Carlier, E. W., and Scofield, C. L., Termination of nerves in capillaries, Jour. of Anat. and Phys., vol. xxii., 1887.

His, W., Ueber embryonale Ganglienzellen, Verh. d. k. Sächs. Gesellsch. d. Wissensch., 1886; Ueber die embryonale Entwickelung der Nervenbahnen, Anat. Anzeiger, 1888.

Hochwart, L. F. v., Ueber De- und Regeneration von Nervenfasern, Wiener medic. Jahrbücher,

1887.

Horsley, V., On the existence of sensory nerves in nerve-trunks (true nervi nervorum) Proc. Roy. Med. Chir. Society, 1884, and Brit. Med. Journal, 1884.

Jacobi, E., Zum feineren Bau der peripheren markhaltigen Nervenfaser, Verhandl. d. phys. med. Gesellsch. zu Würzburg, 1886.

Jakimovitch, J., Sur la structure du cylindre-axe et des cellules nerveuses, Journal de l'anatomie,

1888.

Joseph, Zur feineren Structur der Nervenfasern, Archiv f. Anat. u. Physiol., 1888. Kerschner, L., Beitrag zur Kenntniss der sensiblen Endorgane, Anatom. Anzeiger, 1888. Kölliker, A. v., Histologische Studien an Batrachierlarren, Zeitschr. f. wissensch. Zoologie, Bd. xliii., 1886; Histologische Mittheilungen, Würzb. Sitzungsber., 1889; Über den feineren Bau des Rückenmarks, Münchener medicinische Wochenschrift, 1890; Zur feineren Anatomie des centralen Nervensystems. Beitrag I. Das Kleinhirn, Zeitschrift für wissenschaftliche Zoologie, Bd. 49, 1890; Beitrag II. Das Rückenmark, Ibid.

Krause, W., Die Nervenendigung in den Froschmuskeln, Internat. Monatsschr. f. Anat. u. Histologie, 1884; Die Endothelscheide der Nervenfasern, Ibid., ii., 1885; Die Nervenendigung im elektrischen organ, Ibid. Bd. iii., 1886; Die Nervenendigung in den Muskeln, Ibid., Bd. v., 1888. Kronthal, P., Histologisches von den grossen Zellen in den Vorderhörnern, Neurologisches Centralb. 1890.

Kühne, W., Neue Untersuchungen über die motorische Nervenendigung, Zeitschr. f. Biologie, Bd. xxiii., 1886; Untersuchung der motorischen Nervenendigung an Durchschnitten und Schnittserien, Verhandl. d. naturh. med. Vereins zu Heidelberg, 1887.

Kühne, W., und Chittenden, R. H., Über das Neuro-keratin, Zeitschrift für Biologie, Ed xxvi., 1889.

Kupffer, C., Ueber den Axencylinder markhaltiger Nervenfasern, Sitzungsber d. math. phys. Klasse d. bayr. Akad. d. Wissensch., 1883.

Kupffer und Boveri, Ueber den Bau der Nervenfasern, Sitzungsber. d. Gesellsch. f. Morphologie u. Physiologie z. München, 1885.

Lachi, Pilade, Contributo alla istogenesi della neuroglia nel midollo spinale del pollo, Atti d. Soc. Tosc. d. Sc. Nat., vol. xi., 1890.

Lavdowski, Ueber den feineren Bau der markhaltigen Nervenfasern, Neurol. Centralbl., 1885. Magini, G., Sur la névroglie et les cellules nerveuses cérébrales chez les fœtus, Archives ital. de biol., t. ix., 1887; Ricerche istologiche sui prolungamenti delle cellule epiteliale dell v., ependima, Bollettino della r. accademia medica di Roma, t. x., 1889; Alcuni nuovi caratteri differenziali d. cellule nervose, Atti d. r. acc. dei Lincei, 1890.

Mays, K., Histo-physiologische Untersuchungen über die Verbreitung der Nerven in den Muskeln, Zeitschr. f. Biologie, Bd. xx., 1884; Ueber Nervenfasertheilungen in den Nervenstämmen der Froschmuskeln, Zeitschr. f. Biologie, Bd. xxii., 1886.

Miura, M., Untersuchungen über die motorischen Nervenendigungen der quergestreiften Muskelfasern, Virchow's Archiv, Bd. 105, 1886.

Mondino, C. Sulla struttura delle fibre nervose midoliate periferiche, Archivio per le scienze mediche, viii., 1884.

Nansen, F., The structure and combination of the histological elements of the central nervous system, Bergen, 1887.

Onanoff, I., S. la nature des faisceaux neuro-musculaires, Comptes rendus d. 1. soc. de Biologie,

1890.

Openchowski, Th. v., Beitrag zur Kenntniss der Nervenendigungen im Herzen, Arch. f. mikr. Anat., Bd. xxii., 1883.

Owsjannikow, Quelques remarques sur la structure des nerfs, Revue des sciences naturelles, publiée par la société des naturalistes à St. Petersbourg, Année i., 1890.

Peyrani, C., Ueber die Degeneration durchschnittener Nervenfasern, Biolog. Centralbl., 1883. Petrone, L. M., Sur la structure des nerfs cérébro-rachidiens, Internat. Monatsschrift f. Anat., Bd. v., 1888.

Porter, W. T., The presence of Ranvier's constrictions in the spinal cord of vertebrates, The Quarterly Journal of Microscopical Science, vol. xxxi., 1890.

Prees, J., Nervi nervorum periphericorum, Arch. slaves de biologie, Bd. iv., 1888.

Purvis, G. C., Note on certain terminal organs resembling touch-corpuscles or end-bulbs in intramuscular connective-tissue of the Skate, The Quarterly Journal of Microscopical Science, vol. xxx., 1890. Ramón y Cajal, S., Sur l'origine et les ramifications des fibres nerveuses de la moelle embryonnaire, Anatomischer Anzeiger, 1890; Sur les fibres nerveuses de la couche granuleuse du cervelet et sur l'evolution des éléments cérébelleux, Internationale Monatsschrift für Anatomie, Bd. vii., 1890.

Ranvier, L., De la névroglie, Arch. de physiologie, 1883; Traité technique d'histologie, 2nd Edition, 1890.

Retzius, G., Der Bau des Axencylinders der Nervenfasern, Biologiska Föreningens Förhandlingar, 1889; Zur Kenntnis der Ganglienzellen des Sympathicus, Biologiska Föreningens Förhandlingar, Stockholm, Bd. 11, 1889; Über die Endigungsweise der Nerven in den Genitalnervenkörperchen des Kaninchens, Internationale Monatsschrift für Anatomie und Physiologie, Bd. vii., 1890 ; Biologische Untersuchungen, Neue Foige, Stockholm, 1891.

Rindskoff, C., Ue. d. Verhalten der Muskelfasern nach Nervendurchschneidung, Inaug. Diss., Bonn, 1890.

Sandmann, G., Ueber die Vertheilung der motorischen Nervenendapparate in den quergestreiften Muskeln der Wirbelthiere, Archiv f. Anat. u. Physiol., Physiol. Abth., 1885.

Sass, A. v., Experimentelle Untersuchungen über die Beziehung der motorischen Ganglienzellen der Medulla Spinalis zu motorischen Nerven, Virchow's Arch., Bd. 117, 1889.

Schiefferdecker, P., Beiträge zur Kenntniss des Baues der Nervenfasern, Archiv f. mikrosk.

Anat., Bd. xxx., 1887; Nachtrag zu meiner Arbeit über den Bau der Nervenfasern, Archiv. f. mikrosk. Anat., Bd. xxxi., 1887.

Schon, Jens, Undersögelser om den periphere markholdige nervenprimitiv traads bygning, Kjöbenhavn, 1884.

Smirnow, Alexis, Die Struktur der Nervenzellen im Sympathicus der Amphibien, Archiv. für mikroskopische Anatomie, Band xxxv., 1890.

Spronck, C. H. H., Bijdrage tot de Kennis van den anving der Schwann'sche scheede aan de spinale zenevwortels, Feestbundel a F. C. Donders, Amsterdam, 1888.

Stirling, W., und Macdonald, J. F., The minute structure of the palatine nerves of the frog and the termination of nerves in blood-vessels and glands, Journ. of Anat. and Phys., vol. xviii., 1883.

Tangl, F., Zur Histologie der gequetschten peripherischen Nerven, Archiv f. mikrosk. Anat., Bd. xxix., 1887.

Teuscher, P., Ueber Degeneration am normalen peripheren Nerven, Arch. f. mikr. Anat., Bd. 36,

1890.

Thoma, R., Bemerkungen über die Vater-Pacini'schen Körperchen der Gefässwand, Virchow's Archiv, Bd. cxvi., 1889.

Trinchese, S., Morfologia delle terminazioni nervose matrici periferiche dei vertebrati, Atti d. R. accad. d. Lincei, 1885; Comment les fibres musculaires en voie de développement s'unissent aux fibres nerveuses? Archives italiennes de biologie, t. vii., 1886.

Vanlair, C., Nouvelles recherches expérimentales sur la régéneration des nerfs, Archives de biologie, t. vi., 1885; De la dérivation des nerfs, Archives de physiol., 1885, No. 6; Sur le trajet et la distribution périphérique des nerfs régénérés, Archives de physiol., 1886.

Vignal, W., Mémoire sur le développement des tubes nerveux chez les embryons des mammifères, Archives de physiologie, 1883; Accroissement en longueur des tubes nerveux, par la formation des seyments intercalaires. Archives de physiologie, 1883; Formation et développement des cellules nerveuses de la moëlle épinière des mammifères, Compt. rend., 1884; Sur le développement des éléments de la moëlle des mammifères, Archives de physiol., 1884.

Weigert, Carl, Bemerkungen über das Neurogliagerüst des menschlichen Centralnervensystems, Anatomischer Anzeiger, 1890.

White, W. H., Observations on the histology and functions of the mammalian sympathetic ganglia, Journal of Physiology, vol. 10, 1889.