Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation
Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation
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DOI：
10.1002/cne.10480
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发表时间：
2002-12-16
影响因子：
2.5
通讯作者：
Raphael, Y
中科院分区：
文献类型：
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作者：
Kanzaki, S;Stöver, T;Raphael, Y
与其他颅神经和许多CNS神经元一样，初级听觉神经元由于失去来自其靶细胞（内毛细胞（IHC））的输入而退化。螺旋神经节细胞（SGCs）的电刺激（ES）已被证明可以提高其存活率。胶质细胞源性神经营养因子（GDNF）也已被证明可以增加IHC损失后SGCs的存活。在这项研究中，GDNF转基因的腺病毒载体（Ad-GDNF和ES）的组合效果进行了测试，在第一次消除IHC后的SGCs。动物组接受Ad-GDNF或ES或两者。将Ad-GDNF转染豚鼠耳蜗，使其在耳蜗内高效表达GDNF。ES处理的动物被植入耳蜗植入电极和慢性刺激。第三组动物接受Ad-GDNF和ES（GDNF/ES）。电诱发听觉脑干反应记录ES治疗的动物在刺激期的开始和结束。在聋后43天处死动物，并准备它们的耳朵用于评估IHC存活和SGC计数。治疗耳的SGC存活率显著高于未治疗耳。GDNF/ES组合比单独的任一种治疗提供了显著更好的SGC密度保持。由于ES参数被优化为最大保护（饱和效应），GDNF进一步增强保护表明GDNF和ES介导的SGC保护的机制至少部分是独立的。我们认为GDNF/ES联合应用可改善人工耳蜗植入者的听觉功能。这些发现可能对预防和治疗其他神经退行性疾病具有重要意义。
As with other cranial nerves and many CNS neurons, primary auditory neurons degenerate as a consequence of loss of input from their target cells, the inner hair cells (IHCs). Electrical stimulation (ES) of spiral ganglion cells (SGCs) has been shown to enhance their survival. Glial cell line-derived neurotrophic factor (GDNF) has also been shown to increase survival of SGCs following IHC loss. In this study, the combined effects of the GDNF transgene delivered by adenoviral vectors (Ad-GDNF and ES were tested on SGCs after first eliminating the IHCs. Animal groups received Ad-GDNF or ES or both. Ad-GDNF was inoculated into the cochlea of gumea pigs after deafening, to overexpress human GDNF. ES-treated animals were implanted with a cochlear implant electrode and chronically stimulated. A third group of animals received both Ad-GDNF and ES (GDNF/ES). Electrically evoked auditory brainstem responses were recorded from ES-treated animals at the start and end of the stimulation period. Animals were sacrificed 43 days after deafening and their ears prepared for evaluation of IHC survival and SGC counts. Treated ears exhibited significantly greater SGC survival than nontreated ears. The GDNF/ES combination provided significantly better preservation of SGC density than either treatment alone. Insofar as ES parameters were optimized for maximal protection (saturated effect), the further augmentation of the protection by GDNF suggests that the mechanisms of GDNF- and ES-mediated SGC protection are, at least in part, independent. We suggest that GDNF/ES combined treatment in cochlear implant recipients will improve auditory perception. These findings may have implications for the prevention and treatment of other neurodegenerative processes.