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

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.