TNF-mimetic peptide mixed with fibrin glue improves peripheral nerve regeneration

Brain Res Bull. 2021 Sep:174:53-62. doi: 10.1016/j.brainresbull.2021.06.001. Epub 2021 Jun 6.

Abstract

Surgical intervention is necessary following nerve trauma. Tubular prostheses can guide growing axons and inserting substances within these prostheses can be positive for the regeneration, making it an alternative for the current standard tools for nerve repair. Our aim was to investigate the effects of fibrin glue BthTL when combined with a synthetic TNF mimetic-action peptide on nerve regeneration. Male Wistar rats suffered left sciatic nerve transection. For repairing, we used empty silicon tubes (n = 10), tubes filled with fibrin glue BthTL (Tube + Glue group, n = 10) or tubes filled with fibrin glue BThTL mixed with TNF mimetic peptide (Tube + Glue + Pep group, n = 10). Animals were euthanized after 45 days. We collected nerves to perform immunostaining (neurofilament, GAP43, S100-β, NGFRp75 and Iba-1), light and transmission electron microscopy (for counting myelinated, unmyelinated and degenerated fibers; and for the evaluation of morphometric aspects of regenerated fibers) and collagen staining. All procedures were approved by local ethics committee (protocol 063/17). Tube + Glue + Pep group showed intense inflammatory infiltrate, higher Iba-1 expression, increased immunostaining for NGFRp75 receptor (which characterizes Schwann cell regenerative phenotype), higher myelin thickness and fiber diameter and more type III collagen deposition. Tube + Glue group showed intermediate results between empty tube and Tube + Glue + Pep groups for anti-NGFRp75 immunostaining, inflammation and collagen; on fiber counts, this group showed more degenerate fibers and fewer unmyelinated axons than others. Empty tube group showed superiority only in GAP43 immunostaining. A combination of BthTL glue and TNF mimetic peptide induced greater axonal regrowth and remyelination.

Keywords: Fibrin glue; Myelin; Nerve repair; Schwann cell; Tubulization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Collagen / metabolism
  • Fibrin Tissue Adhesive*
  • Immunohistochemistry
  • Male
  • Myelin Sheath / drug effects
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Regeneration / drug effects*
  • Nerve Tissue Proteins / metabolism
  • Peptidomimetics / administration & dosage*
  • Peptidomimetics / chemistry
  • Peptidomimetics / pharmacology*
  • Peripheral Nerves / drug effects*
  • Rats
  • Rats, Wistar
  • Schwann Cells / drug effects
  • Schwann Cells / ultrastructure
  • Sciatic Nerve / injuries
  • Tumor Necrosis Factor-alpha / administration & dosage*
  • Tumor Necrosis Factor-alpha / chemistry
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Fibrin Tissue Adhesive
  • Nerve Tissue Proteins
  • Peptidomimetics
  • Tumor Necrosis Factor-alpha
  • Collagen