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

Gene Therapy volume 13, pages 296–303 (2006)Cite this article

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.

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Acknowledgements

This work was supported in part by a Grant-in-aid for Scientific Research for Encouragement of Young Scientists (B) (No.14770921), a Grant-in-Aid for Scientific Research (C) (No. 15591831) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a National Grant-in-Aid for the Establishment of High-Tech Research Center in a Private University. A summary of this work was presented in a Research Forum at the 2004 Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery in New York, NY, September 19–22, 2004.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjukuku, Tokyo, Japan

    K Araki, A Shiotani, K Saito, K Moro & K Ogawa

  2. Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan

    K Watabe

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  1. K Araki
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Correspondence to A Shiotani.

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Araki, K., Shiotani, A., Watabe, K. et al. Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury. Gene Ther 13, 296–303 (2006). https://doi.org/10.1038/sj.gt.3302665

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