title: Blockade of glial-derived neurotrophic factor in laryngeal muscles promotes appropriate reinnervation.
abstract: Synkinetic reinnervation of the laryngeal muscles is one of the causes of the poor functional recovery after a recurrent laryngeal nerve (RLN) injury. Glial-derived neurotrophic factor (GDNF) is elevated in rat laryngeal muscles during RLN reinnervation. The specific aim of this investigation was to evaluate the effect of anti-GDNF on RLN reinnervation.
  
  
  
  Anti-GDNF antibody was injected into the posterior cricoarytenoid (PCA) 3 days following RLN transection and anastomosis. Larynges were harvested at 7, 14, 28, 56, and 112 days post injury (DPI). Prior to sacrifice, the vocal fold mobility was assessed. Immunostaining to identify neuromuscular junctions was used to evaluate the extent of axonal reinnervation of the PCA, lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA).
  
  
  
  After anti-GDNF injection into PCA, RLN reinnervation in all muscles was altered when compared to the controls. PCA innervation was delayed. At 7 DPI, only a few axons made synapses in the PCA. In contrast, axons prematurely innervated the LTA and MTA when compared to controls. Innervation was similar to controls at 56 and 112 DPI. Vocal fold motion was enhanced in 10 of 24 animals studied.
  
  
  
  After injection of anti-GDNF into the PCA, early arriving axons bypass the PCA and enter the LTA. Later arriving axons innervate the PCA and MTA. Vocal fold function is improved as compared to controls. Anti-GDNF injection into the PCA influences the pattern of reinnervation and may result in less synkinetic, more functional innervation.
  
  
  
  NA Laryngoscope, 126:E337-E342, 2016.
authors.affiliation: Department of Anatomy and Cell Biology, New York Medical College, Valhalla, New York.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Hernandez-Morato
authors.affiliation: Department of Anatomy and Cell Biology, New York Medical College, Valhalla, New York.
authors.forename: Ishan
authors.initials: I
authors.lastname: Tewari
authors.affiliation: Department of Anatomy and Cell Biology, New York Medical College, Valhalla, New York.
authors.forename: Sansar
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Otolaryngology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, U.S.A. mpitman@nyee.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pitman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001369:Axons / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D007273:Injections, Intramuscular; D007821:Laryngeal Muscles / Q000294:innervation* / Q000378:metabolism; D061224:Laryngeal Nerve Injuries / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012009:Recurrent Laryngeal Nerve / Q000503:physiopathology; D014827:Vocal Cords / Q000503:physiopathology
chemical_list: D000906:Antibodies; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor
keywords: Glial-derived neurotrophic factor; nerve injury; recurrent laryngeal nerve; reinnervation