Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection

BackgroundFollowing transection, nerve repair using the polylactic acid (PLA) conduit is an effective option. In addition, inosine treatment has shown potential to promote nerve regeneration. Therefore, this study aimed to investigate the regenerative potential of inosine after nerve transection and...

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Main Authors: Fellipe Soares dos Santos Cardoso, Guilherme dos Santos Maria, Fernanda Marques Pestana, Ricardo Cardoso, Bruna dos Santos Ramalho, Luiza dos Santos Heringer, Tiago Bastos Taboada, Ana Maria Blanco Martinez, Fernanda Martins de Almeida
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2024.1525024/full
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author Fellipe Soares dos Santos Cardoso
Guilherme dos Santos Maria
Fernanda Marques Pestana
Ricardo Cardoso
Bruna dos Santos Ramalho
Bruna dos Santos Ramalho
Luiza dos Santos Heringer
Tiago Bastos Taboada
Ana Maria Blanco Martinez
Fernanda Martins de Almeida
Fernanda Martins de Almeida
author_facet Fellipe Soares dos Santos Cardoso
Guilherme dos Santos Maria
Fernanda Marques Pestana
Ricardo Cardoso
Bruna dos Santos Ramalho
Bruna dos Santos Ramalho
Luiza dos Santos Heringer
Tiago Bastos Taboada
Ana Maria Blanco Martinez
Fernanda Martins de Almeida
Fernanda Martins de Almeida
author_sort Fellipe Soares dos Santos Cardoso
collection DOAJ
description BackgroundFollowing transection, nerve repair using the polylactic acid (PLA) conduit is an effective option. In addition, inosine treatment has shown potential to promote nerve regeneration. Therefore, this study aimed to investigate the regenerative potential of inosine after nerve transection and polylactic acid conduit repair.MethodsC57/Black6 mice were subjected to sciatic nerve transection, repair with PLA conduit, and intraperitoneal injection of saline or inosine 1 h after injury and daily for 1 week. To assess motor and sensory recovery, functional tests were performed before and weekly up to 8 weeks after injury. Following, to evaluate the promotion of regeneration and myelination, electroneuromyography, morphometric analysis and immunohistochemistry were then performed.ResultsOur results showed that the inosine group had a greater number of myelinated nerve fibers (1,293 ± 85.49 vs. 817 ± 89.2), an increase in neurofilament high chain (NFH) and myelin basic protein (MBP) immunolabeling and a greater number of fibers within the ideal g-ratio (453.8 ± 45.24 vs. 336.6 ± 37.01). In addition, the inosine group presented a greater adenosine A2 receptor (A2AR) immunolabeling area. This resulted in greater compound muscle action potential amplitude and nerve conduction velocity, leading to preservation of muscle and neuromuscular junction integrity, and consequently, the recovery of motor and sensory function.ConclusionOur findings suggest that inosine may enhance regeneration and improve both motor and sensory function recovery after nerve transection when repaired with a poly-lactic acid conduit. This advances the understanding of biomaterials and molecular treatments.
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spelling doaj-art-626724e069a14163afcb0cdbf76d557a2025-01-06T06:59:21ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022025-01-011810.3389/fncel.2024.15250241525024Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transectionFellipe Soares dos Santos Cardoso0Guilherme dos Santos Maria1Fernanda Marques Pestana2Ricardo Cardoso3Bruna dos Santos Ramalho4Bruna dos Santos Ramalho5Luiza dos Santos Heringer6Tiago Bastos Taboada7Ana Maria Blanco Martinez8Fernanda Martins de Almeida9Fernanda Martins de Almeida10Laboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilLaboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilLaboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilFaculdade Souza Marques, Rio de Janeiro, BrazilLaboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilFaculdade Souza Marques, Rio de Janeiro, BrazilLaboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilLaboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilLaboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilLaboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, HUCFF/UFRJ, Rio de Janeiro, BrazilDepartamento de Histologia ICB/UFRJ, Instituto de Ciências Biomédicas, Rio de Janeiro, BrazilBackgroundFollowing transection, nerve repair using the polylactic acid (PLA) conduit is an effective option. In addition, inosine treatment has shown potential to promote nerve regeneration. Therefore, this study aimed to investigate the regenerative potential of inosine after nerve transection and polylactic acid conduit repair.MethodsC57/Black6 mice were subjected to sciatic nerve transection, repair with PLA conduit, and intraperitoneal injection of saline or inosine 1 h after injury and daily for 1 week. To assess motor and sensory recovery, functional tests were performed before and weekly up to 8 weeks after injury. Following, to evaluate the promotion of regeneration and myelination, electroneuromyography, morphometric analysis and immunohistochemistry were then performed.ResultsOur results showed that the inosine group had a greater number of myelinated nerve fibers (1,293 ± 85.49 vs. 817 ± 89.2), an increase in neurofilament high chain (NFH) and myelin basic protein (MBP) immunolabeling and a greater number of fibers within the ideal g-ratio (453.8 ± 45.24 vs. 336.6 ± 37.01). In addition, the inosine group presented a greater adenosine A2 receptor (A2AR) immunolabeling area. This resulted in greater compound muscle action potential amplitude and nerve conduction velocity, leading to preservation of muscle and neuromuscular junction integrity, and consequently, the recovery of motor and sensory function.ConclusionOur findings suggest that inosine may enhance regeneration and improve both motor and sensory function recovery after nerve transection when repaired with a poly-lactic acid conduit. This advances the understanding of biomaterials and molecular treatments.https://www.frontiersin.org/articles/10.3389/fncel.2024.1525024/fullnerve repairinosinesciatic nerve transectionnerve regenerationA2A receptor
spellingShingle Fellipe Soares dos Santos Cardoso
Guilherme dos Santos Maria
Fernanda Marques Pestana
Ricardo Cardoso
Bruna dos Santos Ramalho
Bruna dos Santos Ramalho
Luiza dos Santos Heringer
Tiago Bastos Taboada
Ana Maria Blanco Martinez
Fernanda Martins de Almeida
Fernanda Martins de Almeida
Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
Frontiers in Cellular Neuroscience
nerve repair
inosine
sciatic nerve transection
nerve regeneration
A2A receptor
title Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
title_full Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
title_fullStr Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
title_full_unstemmed Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
title_short Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
title_sort nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
topic nerve repair
inosine
sciatic nerve transection
nerve regeneration
A2A receptor
url https://www.frontiersin.org/articles/10.3389/fncel.2024.1525024/full
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