gms | German Medical Science

68th Annual Meeting of the German Society of Neurosurgery (DGNC)
7th Joint Meeting with the British Neurosurgical Society (SBNS)

German Society of Neurosurgery (DGNC)

14 - 17 May 2017, Magdeburg

Analysis of axonal regeneration, remyelination and guidance in human neuroma

Meeting Abstract

  • Patrick Dömer - Universitätsklinik für Neurochirurgie, Medizinischer Campus Carl-von-Ossietzky-Universität Oldenburg, Oldenburg, Deutschland
  • Bettina Kewitz - Universitätsklinik für Neurochirurgie, Medizinischer Campus Carl-von-Ossietzky-Universität Oldenburg, Oldenburg, Deutschland
  • Christian Heinen - Universitätsklinik für Neurochirurgie, Medizinischer Campus Carl-von-Ossietzky-Universität Oldenburg, Evangelisches Krankenhaus, Oldenburg, Deutschland
  • Ulrike Janssen-Bienhold - Department of Neuroscience, School of Medicine and Health Sciences, Faculty VI, University of Oldenburg, Oldenburg, Deutschland
  • Thomas Kretschmer - Evangelisches Krankenhaus Oldenburg, Universitätsklinik für Neurochirurgie, Oldenburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocMO.25.06

doi: 10.3205/17dgnc154, urn:nbn:de:0183-17dgnc1540

Published: June 9, 2017

© 2017 Dömer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at



Objective: Neuromas are pathologic nerve distensions caused by a nerve’s response to trauma. Sprouting axons attempt to cross the injury site, as long as scar tissue, a gap or lacking axonal guidance do not counteract sprouting. If target-oriented sprouting is prevented a neuroma in-continuity or discontinuity will form. So far, rat models have shown that regeneration associated genes play an important role for axonal regeneration. Furthermore, endoneurial tubes providing axonal guidance are crucial for successful regeneration. On a molecular scale, however the precise sequence has not been resolved for human nerve. Therefore, human neuroma formation, its influencing factors and the neuroma composition are of interest.

Methods: Axonal sprouting, the formation of endoneurial tubes and the status of myelination was analyzed in six human neuromas. Neuroma tissue was obtained from nerve grafted patients during surgery. Tissue samples were prepared directly in the OR for fixation (2% PFA, over night) or frozen at -80°C immediately after resection. For immunochemistry, cryosections (20 µm) were blocked (10% NGS, 1h) and incubated with primary antibodies (ABs) over night (4°C). Corresponding fluorochrome conjugated ABs were applied at RT for 2h. Analysis of the axon count was carried out using ImageJ (paired t-test).

Results: NF-immunoreactivity patterns indicate a significant reduction of axons from the proximal to the distal segment of each neuroma (neuroma in-continuity: p= 0.0007, stump neuroma: p= 0.0001). Beside NF-containing nerve fibers, axons expressing large amounts of Gap43 were detected. Axonal growth cones labeled with Gap43 antibodies sprout along NF-positive fibers in a piggyback-like manner. Double labeling of Gap43 immunoreactive axons and the myelin-sheath (MBP) indicate a remyelination of sprouting axons by Schwann cells in the neuromatous tissue. Mini-fascicles of regenerating axons were ensheathed by NG2 positive endoneurial tube like structures in the neuromatous tissue, whereas NG2-immunoreactivity was absent proximal and distal to the neuroma. There seem to be no differences in the molecular and cellular architecture between stump neuroma and neuroma in-continuity.

Conclusion: The extensive expression of Gap43 underlines the remaining regenerative potential and axonal plasticity of regenerating axons within the neuroma. Furthermore, myelination of Gap43-positive axons suggests that the capability of Schwann cells to remyelinate regenerating axons is preserved in neuroma tissue. Therefore, unsuccessful regeneration may be more likely related to the lack of and failure to connect to persistent endoneurial tubes distal to the neuroma and thus, disruption of axonal guidance to the target organ. Correlation of results to corresponding clinical findings (e.g. age, latency, functional outcome) will help to improve surgical strategy including timing.