Extracorporeal shockwave therapy accelerates motor axon regeneration despite a phenotypically mismatched environment
Introduction: Peripheral nerve injuries are common and a frequent cause of hospitalization displaying a major burden to patients and social health-care systems1. Although regeneration after autologous nerve transplantation has been the target of scientific curiosity since the beginning of modern medicine, not much progress in accelerating this tedious process has been made23. A possible explanation could be the experimental model chosen. Most research groups use the sciatic nerve defect as a model for autologous nerve transplantation, dismissing the influence of phenotypically different nerve grafts on regeneration4. We thus hypothesize that this mismatch has a negative influence on motor axonal regeneration and that extracorporeal shockwave therapy (ESWT) can ameliorate this effect. Our first aim is to establish a modified femoral nerve defect model reflecting the phenotypical difference of transplanted autologous nerve grafts in the clinic. Second, we aim to evaluate the effect of ESWT, which has been shown to be one of very few treatment options accelerating peripheral nerve regeneration, in this model.
Methods: Adult male Sprague Dawley rats were divided in groups of at least 8 animals. A 6 mm autologous nerve transplantation was performed using either homotopic (matched) or heterotopic grafting. The treatment group received directly after wound closure ESWT (300 impulses, 3 Hz, 0,1mJ/mm2). The effects of ESWT on the regenerating motor fibers have been evaluated functionally, histologically, and by gene expression analysis via qPCR.
Results: Motor nerves show less than 50% expression of pro-proliferative markers (Ki67, p75) in early stages of neuronal regeneration than sensory nerves. Furthermore, electrophysiological as well as histological evaluations indicate slower regeneration of motor axons in the heterotopic setting when compared to the homotopic grafting. ESWT increases expression of markers for re-myelination (Cadm3 and Cadm4) and homeostasis (TrkB) up to 100% 6 weeks after injury in both groups, indicating amelioration of negative effects of phenotypical mismatch.
Conclusion: This study shows that ESWT is able to accelerate peripheral nerve regeneration in a successfully modified femoral nerve model which reflects the clinical reality after autologous nerve transplantation. Hereby, providing support for the use of ESWT after surgical repair of peripheral nerve injuries.
Methods: Adult male Sprague Dawley rats were divided in groups of at least 8 animals. A 6 mm autologous nerve transplantation was performed using either homotopic (matched) or heterotopic grafting. The treatment group received directly after wound closure ESWT (300 impulses, 3 Hz, 0,1mJ/mm2). The effects of ESWT on the regenerating motor fibers have been evaluated functionally, histologically, and by gene expression analysis via qPCR.
Results: Motor nerves show less than 50% expression of pro-proliferative markers (Ki67, p75) in early stages of neuronal regeneration than sensory nerves. Furthermore, electrophysiological as well as histological evaluations indicate slower regeneration of motor axons in the heterotopic setting when compared to the homotopic grafting. ESWT increases expression of markers for re-myelination (Cadm3 and Cadm4) and homeostasis (TrkB) up to 100% 6 weeks after injury in both groups, indicating amelioration of negative effects of phenotypical mismatch.
Conclusion: This study shows that ESWT is able to accelerate peripheral nerve regeneration in a successfully modified femoral nerve model which reflects the clinical reality after autologous nerve transplantation. Hereby, providing support for the use of ESWT after surgical repair of peripheral nerve injuries.
