Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury

K. Araki, A. Shiotani, K. Watabe, Koichiro Saito, K. Moro, K. Ogawa

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

To assess the possibility of gene therapy for recurrent laryngeal nerve (RLN) injury, we examined functional and histological recovery after glial cell line-derived neurotrophic factor (GDNF) gene transfer in a rat RLN crush model. Adenoviral vector encoding β-galactosidase gene (AxCALacZ) or human GDNF gene (AxCAhGDNF) was injected into the crush site of the RLN. Neurons in the nucleus ambiguus on the crushed side were labeled with X-gal or GDNF immnohistochemistry after AxCALacZ or AxCAhGDNF injection. Reverse transcription-polymerase chain reaction analysis revealed expression of human GDNF mRNA transcripts in brainstem tissue containing the nucleus ambiguus on the crushed side after AxCAhGDNF injection. Animals injected with AxCAhGDNF displayed significantly improved motor nerve conduction velocity of the RLN and recovery rate of vocal fold movement at 2 and 4 weeks after treatment as compared to controls. AxCAhGDNF-injected animals showed a significantly larger axonal diameter and improved remyelination in crushed RLN as compared to controls. Adenoviral GDNF gene transfer may thus promote laryngeal function recovery after RLN injury. Inoculation of adenoviral vector containing the GDNF gene at the site of damage soon after nerve injury may assist patients with laryngeal paralysis caused by nerve injury during head and neck surgery.

Original languageEnglish
Pages (from-to)296-303
Number of pages8
JournalGene Therapy
Volume13
Issue number4
DOIs
Publication statusPublished - 2006 Feb 1

Keywords

  • Adenovirus
  • Cranial nerve injury
  • GDNF
  • Nucleus ambiguus
  • Recurrent laryngeal nerve
  • Vocal fold palsy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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