Analysis of regeneration- and myelination-associated proteins in human neuroma in continuity and discontinuity
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.
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.
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.
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.
KeywordsNeuroma Peripheral nerve Regeneration Myelination Nerve injury
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.
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.
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.
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