Appropriate dosage, timing, and site of intramuscular injections of brain‐derived neurotrophic factor (BDNF) promote motor recovery after facial nerve injury in rats

Abstract

AbstractIntroduction/AimsDaily intramuscular injections of fibroblast growth factor 2 (FGF2) but not of brain‐derived neurotrophic factor (BDNF) significantly improve whisking behavior and mono‐innervation of the rat levator labii superioris (LLS) muscle 56 days after buccal nerve transection and suture (buccal–buccal anastomosis, BBA). We explored the dose–response of BDNF, FGF2, and insulin growth factor 2 (IGF2) on the same parameters, asking whether higher doses of BDNF would promote recovery.MethodsAfter BBA, growth factors were injected (30 μL volume) daily into the LLS muscle over 14, 28, or 56 days. At 56 days, video‐based motion analysis of vibrissal whisking was performed and the extent of mono‐ and poly‐reinnervation of the reinnervated neuromuscular junctions (NMJs) of the muscle determined with immunostaining of the nerve with β‐tubulin and histochemical staining of the endplates with Alexa Fluor 488‐conjugated α‐bungarotoxin.ResultsThe dose–response curve demonstrated significantly higher whisking amplitudes and corresponding increased mono‐innervation of the NMJ in the reinnervated LLS muscle at concentrations of 20–30 μg/mL BDNF administered daily for 14–28 days after BBA surgery. In contrast, high doses of IGF2 and FGF2, or doses of 20 and 40 μg/mL of BDNF administered for 14–56 days had no effect on either whisking behavior or in reducing poly‐reinnervation of endplates in the muscle.DiscussionThese data suggest that the re‐establishment of mono‐innervation of whiskerpad muscles and the improved motor function by injections of BDNF into the paralyzed vibrissal musculature after facial nerve injury have translation potential and promote clinical application.