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Acetylcholine receptors of the neuromuscular junctions present normal distribution after peripheral nerve injury and repair through nerve guidance associated with fibrin biopolymer

  • Ana Paula Silveira Leite
    Correspondence
    Corresponding author at: Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp). Rua Professor Doutor Antonio Celso Wagner Zanin, 250, Unesp Campus de Botucatu, Botucatu, SP, Brazil.
    Affiliations
    Medical School, São Paulo State University (Unesp), Botucatu, SP, Brazil

    Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Carina Guidi Pinto
    Affiliations
    Medical School, São Paulo State University (Unesp), Botucatu, SP, Brazil

    Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Felipe Cantore Tibúrcio
    Affiliations
    Medical School, São Paulo State University (Unesp), Botucatu, SP, Brazil

    Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Kevin Silva Muller
    Affiliations
    Medical School, São Paulo State University (Unesp), Botucatu, SP, Brazil

    Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Carlos Roberto Padovani
    Affiliations
    Division of Biostatistics, Department of Biostatistics, Vegetal Biology, Parasitology and Zoology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Benedito Barraviera
    Affiliations
    Medical School, São Paulo State University (Unesp), Botucatu, SP, Brazil

    Center for the Study of Venoms and Venomous Animals (Cevap), São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Rui Seabra Ferreira Junior
    Affiliations
    Center for the Study of Venoms and Venomous Animals (Cevap), São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Claudenete Vieira Leal
    Affiliations
    School of Mechanical Engineering, University of Campinas (Unicamp), Campinas, SP, Brazil
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  • Cintia Yuri Matsumura
    Affiliations
    Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu, SP, Brazil
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  • Selma Maria Michelin Matheus
    Affiliations
    Division of Anatomy, Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (Unesp), Botucatu, SP, Brazil
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Published:November 22, 2022DOI:https://doi.org/10.1016/j.injury.2022.11.047

      Highlights

      • NMJs of TB+FB group presented morphological and morphometric approximation (compactness index; area of the AChRs and motor plate) to the S group.
      • Also, on TB+FB group there was a Schwann cell increase even 90 days after the peripheral nerve injury.
      • The use of PCL and FB combined on the tubulization technique provided nerve regeneration improvement and NMJ structure maintenance.

      Abstract

      Peripheral nerve injuries (PNI) lead to alterations in the Agrin-LRP4-MuSK pathway. This results in disaggregation of AChRs and change from epsilon (mature, innervated) to gamma (immature, denervated) subunit. Tubulization technique has been shown to be effective for PNI repair and it also allows the use of adjuvants, such as fibrin biopolymer (FB). This study evaluated the effect of the association of tubulization with FB after PNI on AChRs and associated proteins. Fifty-two adults male Wistar rats were used, distributed in 4 experimental groups: Sham Control (S), Denervated Control (D); Tubulization (TB) and Tubulization + Fibrin Biopolymer (TB+FB). Catwalk was performed every 15 days. Ninety days after surgery the right soleus muscles and ischiatic nerves were submitted to the following analyses: (a) morphological and morphometric analysis of AChRs by confocal microscopy; (b) morphological and morphometric analysis of the ischiatic nerve; (c) protein quantification of AChRs: alpha, gama, and epsilon, of Schwann cells, agrin, LRP4, MuSK, rapsyn, MMP3, MyoD, myogenin, MURF1 and atrogin-1. The main results were about the NMJs that in the TB+FB group presented morphological and morphometric approximation (compactness index; area of the AChRs and motor plate) to the S group. In addition, there were also an increase of S100 and AChRε protein expression and a decrease of MyoD. These positive association resulted in AChRs stabilization that potentiate the neuromuscular regeneration, which strengthens the use of TB for severe injuries repair and the beneficial effect of FB, along with tubulization technique.

      Keywords

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