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

K. Araki; A. Shiotani; K. Watabe; K. Saito; K. Moro; K. Ogawa

doi:10.1038/sj.gt.3302665

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

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

Research output: Contribution to journal › Article › peer-review

51 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 language	English
Pages (from-to)	296-303
Number of pages	8
Journal	Gene Therapy
Volume	13
Issue number	4
DOIs	https://doi.org/10.1038/sj.gt.3302665
Publication status	Published - 2006 Feb
Externally published	Yes

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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10.1038/sj.gt.3302665

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title = "Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury",

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.",

keywords = "Adenovirus, Cranial nerve injury, GDNF, Nucleus ambiguus, Recurrent laryngeal nerve, Vocal fold palsy",

author = "K. Araki and A. Shiotani and K. Watabe and K. Saito and K. Moro and K. Ogawa",

note = "Funding Information: 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.",

year = "2006",

month = feb,

doi = "10.1038/sj.gt.3302665",

language = "English",

volume = "13",

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T1 - Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury

AU - Araki, K.

AU - Shiotani, A.

AU - Watabe, K.

AU - Saito, K.

AU - Moro, K.

AU - Ogawa, K.

N1 - Funding Information: 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.

PY - 2006/2

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N2 - 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.

AB - 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.

KW - Adenovirus

KW - Cranial nerve injury

KW - GDNF

KW - Nucleus ambiguus

KW - Recurrent laryngeal nerve

KW - Vocal fold palsy

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

Abstract

Keywords

ASJC Scopus subject areas

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