Neutralizing BDNF and FGF2 injection into denervated skeletal muscle improve recovery after nerve repair

Muscle Nerve. 2020 Sep;62(3):404-412. doi: 10.1002/mus.26991. Epub 2020 Jun 18.

Abstract

Background: After facial nerve injury and surgical repair in rats, recovery of vibrissal whisking is associated with a high proportion of mono-innervated neuro-muscular junctions (NMJs). Our earlier work with Sprague Dawley (SD)/Royal College of Surgeons (RCS) rats, which are blind and spontaneously restore NMJ-monoinnervation and whisking, showed correlations between functional recovery and increase of fibroblast growth factor-2 (FGF2) and brain-derived neurotrophic factor (BDNF) in denervated vibrissal muscles.

Methods: We used normally sighted rats (Wistar), in which NMJ-polyinnervation is highly correlated with poor whisking recovery, and injected the vibrissal muscle levator labii superioris (LLS) with combinations of BDNF, anti-BDNF, and FGF2 at different postoperative periods after facial nerve injury.

Results: Rats receiving anti-BDNF+FGF2 showed low NMJ-polyinnervation and best recovery of whisking amplitude.

Conclusions: Restoration of target reinnervation after peripheral nerve injury requires a complex mixture of trophic factors with a specific time course of availability for each of them.

Keywords: BDNF; FGF2; axotomy; functional recovery; motoneuron; motor endplates; polyinnervation; vibrissae whisking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / therapeutic use*
  • Brain-Derived Neurotrophic Factor / immunology*
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Denervation
  • Facial Muscles / drug effects
  • Facial Muscles / innervation
  • Facial Muscles / physiopathology
  • Facial Nerve Injuries / drug therapy*
  • Facial Nerve Injuries / physiopathology
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / therapeutic use*
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*
  • Vibrissae / physiology*

Substances

  • Antibodies, Neutralizing
  • Brain-Derived Neurotrophic Factor
  • Fibroblast Growth Factor 2