Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury
Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury
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DOI：
10.1038/sj.gt.3302665
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发表时间：
2006-02-01
期刊：
影响因子：
5.1
通讯作者：
Ogawa, K
中科院分区：
文献类型：
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作者：
Araki, K;Shiotani, A;Ogawa, K
为了评估基因治疗喉返神经（RLN）损伤的可能性，我们研究了胶质细胞源性神经营养因子（GDNF）基因转移后的功能和组织学恢复在大鼠RLN挤压模型。将编码β-半乳糖苷酶基因（AxCALacZ）或人GDNF基因（AxCAhGDNF）的腺病毒载体注射到RLN的挤压部位。注射AxCALacZ或AxCAhGDNF后，用X-gal或GDNF免疫组化标记压伤侧疑核神经元。逆转录-聚合酶链反应分析显示，人GDNF mRNA转录本的表达在脑干组织中含有核疑的破碎后AxCAhGDNF注射侧。与对照组相比，注射AxCAhGDNF的动物在治疗后2周和4周显示出显著改善的RLN的运动神经传导速度和声带运动的恢复率。与对照组相比，AxCAhGDNF注射的动物显示出显著更大的轴突直径和改善的压碎的RLN中的髓鞘再生。腺病毒GDNF基因转移可促进喉返神经损伤后喉功能的恢复。在神经损伤后不久，在损伤部位接种含有GDNF基因的腺病毒载体可能有助于头颈部手术中神经损伤引起的喉麻痹患者。
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 beta-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.