Axonal regeneration and innervation ratio following supercharged end-to-side nerve transfer
IntroductionPeripheral nerve injuries often result in incomplete recovery, particularly after the occurrence of proximal lesions, owing to the extended reinnervation time as well as consequent reductions in the regeneration supportive factors and muscle recovery potential. In these cases, supercharg...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1513321/full |
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| author | Leopold Harnoncourt Martin Schmoll Christopher Festin Laurenz Pflaum Markus Breuss Johanna Klepetko Dominik C. Dotzauer Florian J. Jaklin Udo Maierhofer Philipp Tratnig-Frankl Oskar C. Aszmann Oskar C. Aszmann |
| author_facet | Leopold Harnoncourt Martin Schmoll Christopher Festin Laurenz Pflaum Markus Breuss Johanna Klepetko Dominik C. Dotzauer Florian J. Jaklin Udo Maierhofer Philipp Tratnig-Frankl Oskar C. Aszmann Oskar C. Aszmann |
| author_sort | Leopold Harnoncourt |
| collection | DOAJ |
| description | IntroductionPeripheral nerve injuries often result in incomplete recovery, particularly after the occurrence of proximal lesions, owing to the extended reinnervation time as well as consequent reductions in the regeneration supportive factors and muscle recovery potential. In these cases, supercharged end-to-side (SETS) nerve transfers preserve the continuity of the original nerves while facilitating additional axonal support to mitigate muscle atrophy. This approach enhances functional recovery and has been demonstrated to be effective in both preclinical models and clinical settings. In this study, a novel SETS nerve transfer model is presented for the upper extremity of the rat to assess the impacts on muscle function, innervation ratio, and motor neuron regeneration as well as investigate the potential to enhance motor function recovery.MethodsThe surgical interventions include transection and end-to-end repair of the musculocutaneous nerve (MCN) in Group A, transfer of the ulnar nerve (UN) to the side of the MCN in Group B, and a combination of both in Group C. The biceps muscle function was assessed 12 weeks post-surgery using electrical stimulation.ResultsMuscle assessments revealed no significant differences in force between the experimental groups. UN-related muscle reinnervation was observed only in Group C after transfer to a regenerating nerve. Retrograde labeling demonstrated motor neuron regeneration of both the MCN and UN in a distal direction toward the muscle; however, tracer uptake of the UN motor neurons following intramuscular tracer application was detected only in Group C. In contrast, stained pseudounipolar cells in the dorsal root ganglia associated with the UN and MCN revealed afferent muscle innervations in Groups B and C.DiscussionThis novel SETS nerve transfer model enables isolated electrophysiological as well as histological evaluations of all nerve sections to determine the muscle innervation ratio exactly. Our findings indicate that substantial functional efferent muscle innervation by the donor nerve is exclusively observed in a regenerating environment. |
| format | Article |
| id | doaj-art-3a1b832724cc475cb22f3b336da2a0ad |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-3a1b832724cc475cb22f3b336da2a0ad2025-02-12T07:25:26ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-02-011310.3389/fcell.2025.15133211513321Axonal regeneration and innervation ratio following supercharged end-to-side nerve transferLeopold Harnoncourt0Martin Schmoll1Christopher Festin2Laurenz Pflaum3Markus Breuss4Johanna Klepetko5Dominik C. Dotzauer6Florian J. Jaklin7Udo Maierhofer8Philipp Tratnig-Frankl9Oskar C. Aszmann10Oskar C. Aszmann11Clinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaClinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, AustriaIntroductionPeripheral nerve injuries often result in incomplete recovery, particularly after the occurrence of proximal lesions, owing to the extended reinnervation time as well as consequent reductions in the regeneration supportive factors and muscle recovery potential. In these cases, supercharged end-to-side (SETS) nerve transfers preserve the continuity of the original nerves while facilitating additional axonal support to mitigate muscle atrophy. This approach enhances functional recovery and has been demonstrated to be effective in both preclinical models and clinical settings. In this study, a novel SETS nerve transfer model is presented for the upper extremity of the rat to assess the impacts on muscle function, innervation ratio, and motor neuron regeneration as well as investigate the potential to enhance motor function recovery.MethodsThe surgical interventions include transection and end-to-end repair of the musculocutaneous nerve (MCN) in Group A, transfer of the ulnar nerve (UN) to the side of the MCN in Group B, and a combination of both in Group C. The biceps muscle function was assessed 12 weeks post-surgery using electrical stimulation.ResultsMuscle assessments revealed no significant differences in force between the experimental groups. UN-related muscle reinnervation was observed only in Group C after transfer to a regenerating nerve. Retrograde labeling demonstrated motor neuron regeneration of both the MCN and UN in a distal direction toward the muscle; however, tracer uptake of the UN motor neurons following intramuscular tracer application was detected only in Group C. In contrast, stained pseudounipolar cells in the dorsal root ganglia associated with the UN and MCN revealed afferent muscle innervations in Groups B and C.DiscussionThis novel SETS nerve transfer model enables isolated electrophysiological as well as histological evaluations of all nerve sections to determine the muscle innervation ratio exactly. Our findings indicate that substantial functional efferent muscle innervation by the donor nerve is exclusively observed in a regenerating environment.https://www.frontiersin.org/articles/10.3389/fcell.2025.1513321/fullperipheral nerve regenerationnerve transfersupercharged end-to-sidereversed end-to-sideinnervation ratio |
| spellingShingle | Leopold Harnoncourt Martin Schmoll Christopher Festin Laurenz Pflaum Markus Breuss Johanna Klepetko Dominik C. Dotzauer Florian J. Jaklin Udo Maierhofer Philipp Tratnig-Frankl Oskar C. Aszmann Oskar C. Aszmann Axonal regeneration and innervation ratio following supercharged end-to-side nerve transfer Frontiers in Cell and Developmental Biology peripheral nerve regeneration nerve transfer supercharged end-to-side reversed end-to-side innervation ratio |
| title | Axonal regeneration and innervation ratio following supercharged end-to-side nerve transfer |
| title_full | Axonal regeneration and innervation ratio following supercharged end-to-side nerve transfer |
| title_fullStr | Axonal regeneration and innervation ratio following supercharged end-to-side nerve transfer |
| title_full_unstemmed | Axonal regeneration and innervation ratio following supercharged end-to-side nerve transfer |
| title_short | Axonal regeneration and innervation ratio following supercharged end-to-side nerve transfer |
| title_sort | axonal regeneration and innervation ratio following supercharged end to side nerve transfer |
| topic | peripheral nerve regeneration nerve transfer supercharged end-to-side reversed end-to-side innervation ratio |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1513321/full |
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