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Acta Neurochirurgica

, Volume 160, Issue 6, pp 1269–1281 | Cite as

Analysis of regeneration- and myelination-associated proteins in human neuroma in continuity and discontinuity

  • Patrick Dömer
  • Bettina Kewitz
  • Christian P. G. Heinen
  • Ulrike Janssen-Bienhold
  • Thomas Kretschmer
Original Article - Peripheral Nerves

Abstract

Background

Neuromas are pathologic nerve distensions caused by a nerve’s response to trauma, resulting in a dysfunctional to non-functional nerve. Depending on the severance of the affected nerve, the resulting neuroma can be differentiated into continuous and stump neuroma. While neuroma formation has been investigated in animal models with enormous regenerative capacity, the search for differences in human response to nerve trauma on a molecular level ultimately seeks to identify reasons for functionally successful versus unsuccessful regeneration after peripheral nerve trauma in man.

Methods

In the present study, the regenerative potential of axons and the capability of Schwann cells (SC) to remyelinate regenerating axons was quantitatively and segmentally analyzed and compared within human neuroma in-continuity and discontinuity.

Results

For the stump neuroma and the neuroma in-continuity, there was a significant reduction of the total number of axons (86% stump neuroma and 91% neuroma in-continuity) from the proximal to the distal part of the neuroma, while the amount of fibrotic tissue increased, respectively. Labeling the myelin sheath of regenerating axons revealed a remyelination of regenerating axons by SCs in both neuroma types. The segmented analysis showed no distinct alterations in the number and spatial distribution of regenerating, mature, and myelinated axons between continuous and discontinuous neuroma.

Conclusions

The quantitative and segmented analysis showed no distinct alterations in the number and spatial distribution of regenerating, mature, and myelinated axons between continuous and discontinuous neuroma, while the extensive expression of Gap43 in up to 55% of the human neuroma axons underlines their regenerative capacity independent of whether the neuroma is in continuity or discontinuity. Remyelination of Gap43-positive axons suggests that the capability of SCs to remyelinate regenerating axons is preserved in neuroma tissue.

Keywords

Neuroma Peripheral nerve Regeneration Myelination Nerve injury 

Notes

Author contributions

TK and UJ-B conceived the project; PD, BK UJ-B, and TK designed the experiments; TK and CH performed the surgery; PD and BK the performed experiments; all contributed to the interpretation of data; PD wrote the article; PD and BK prepared the figures; and all authors edited and commented on the manuscript.

Funding

The project was generously supported by an intramural fund of faculty VI of the Carl-von-Ossietzky University Oldenburg to Thomas Kretschmer (Forschungspoolförderung für Projekt “Molekularbiologische Untersuchungen an humanen Neuromen”).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was carried out in accordance with the local ethics committee with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki.

Supplementary material

701_2018_3544_Fig12_ESM.gif (86 kb)
Supplementary Figure 1

Overview of the distribution of NF, Gap43 and MBP positive axons in the different segments of the neuromas in-continuity (A-C) and neuromas in-discontinuity (D-F). For the stump neuroma (n = 3) and the neuroma in-continuity (n = 3), 10 ROIs were counted for each neuroma segment. Results are expressed as mean ± SEM. (GIF 85 kb).

701_2018_3544_MOESM1_ESM.tif (3.6 mb)
High Resolution Image (TIFF 3678 kb).
701_2018_3544_Fig13_ESM.gif (56 kb)
Supplementary Figure 2

Full-length immunoblots of NF-200, Gap43 and MBP in the different segments of the neuroma in-continuity. The specific immunoreactive bands are highlighted by red arrows. (GIF 55 kb).

701_2018_3544_MOESM2_ESM.tif (6.4 mb)
High Resolution Image (TIFF 6588 kb).

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurosurgery, School of Medicine and Health Sciences, Faculty VIUniversity of OldenburgOldenburgGermany
  2. 2.Department of Neuroscience, School of Medicine and Health Sciences, Faculty VIUniversity of OldenburgOldenburgGermany
  3. 3.Department of Neurosurgery, Klinikum Klagenfurt am WSKlagenfurtAustria

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