title: A combination of Schwann-cell grafts and aerobic exercise enhances sciatic nerve regeneration.
abstract: BACKGROUND
  Despite the regenerative potential of the peripheral nervous system, severe nerve lesions lead to loss of target-organ innervation, making complete functional recovery a challenge. Few studies have given attention to combining different approaches in order to accelerate the regenerative process.
  
  
  OBJECTIVE
  Test the effectiveness of combining Schwann-cells transplantation into a biodegradable conduit, with treadmill training as a therapeutic strategy to improve the outcome of repair after mouse nerve injury.
  
  
  METHODS
  Sciatic nerve transection was performed in adult C57BL/6 mice; the proximal and distal stumps of the nerve were sutured into the conduit. Four groups were analyzed: acellular grafts (DMEM group), Schwann cell grafts (3×105/2 µL; SC group), treadmill training (TMT group), and treadmill training and Schwann cell grafts (TMT + SC group). Locomotor function was assessed weekly by Sciatic Function Index and Global Mobility Test. Animals were anesthetized after eight weeks and dissected for morphological analysis.
  
  
  RESULTS
  Combined therapies improved nerve regeneration, and increased the number of myelinated fibers and myelin area compared to the DMEM group. Motor recovery was accelerated in the TMT + SC group, which showed significantly better values in sciatic function index and in global mobility test than in the other groups. The TMT + SC group showed increased levels of trophic-factor expression compared to DMEM, contributing to the better functional outcome observed in the former group. The number of neurons in L4 segments was significantly higher in the SC and TMT + SC groups when compared to DMEM group. Counts of dorsal root ganglion sensory neurons revealed that TMT group had a significant increased number of neurons compared to DMEM group, while the SC and TMT + SC groups had a slight but not significant increase in the total number of motor neurons.
  
  
  CONCLUSIONS
  These data provide evidence that this combination of therapeutic strategies can significantly improve functional and morphological recovery after sciatic injury.
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Camila Oliveira
authors.initials: CO
authors.lastname: Goulart
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Sofia
authors.initials: S
authors.lastname: Jürgensen
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Allana
authors.initials: A
authors.lastname: Souto
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Júlia Teixeira
authors.initials: JT
authors.lastname: Oliveira
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Silmara
authors.initials: S
authors.lastname: de Lima
authors.affiliation: Department of Mechanics, Politecnico di Torino, Turin, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tonda-Turo
authors.affiliation: Instituto de Biologia, Departamento de Neurobiologia, Laboratório de Regeneração Neural e Função, UFF, Rio de Janeiro, Brazil.
authors.forename: Suelen Adriani
authors.initials: SA
authors.lastname: Marques
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil; Pólo Universitário Macaé, UFRJ, Macaé, RJ, Brazil.
authors.forename: Fernanda Martins
authors.initials: FM
authors.lastname: de Almeida
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, HUCFF, UFRJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Maria Blanco
authors.initials: AM
authors.lastname: Martinez
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002470:Cell Survival; D017690:Cell Transplantation; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration; D009469:Neuromuscular Junction; D059348:Peripheral Nerve Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D010805:Physical Conditioning, Animal; D011091:Polyesters / Q000378:metabolism; D020127:Recovery of Function; D012583:Schwann Cells / Q000166:cytology*; D012584:Sciatic Nerve / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D009414:Nerve Growth Factors; D011091:Polyesters; C016240:polycaprolactone