Department of Otorhinolaryngology and Head & Neck Surgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
Hear Res. 2012 Jun;288(1-2):19-33. doi: 10.1016/j.heares.2012.03.002. Epub 2012 Mar 21.
Spiral ganglion cell (SGC) degeneration following hair cell loss can be prevented by administration of exogenous neurotrophic factors. Many of these neurotrophic factors, in particular the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been described to be involved in the development of the rodent cochlea. While expression of most of the neurotrophins has decreased to below detectable levels during adulthood (only NT-3 remains highly expressed), their respective receptors remain present in SGCs. Indeed much less is known about the function of neurotrophins in the mature cochlea. Such knowledge is crucial in the search for tools to improve SGC survival following cochlear implantation. In this review, we will critically regard the current experimental findings of neurotrophic treatment of the SGCs in the perspective of fundamental cellular mechanisms underlying neurotrophin signaling. We conclude that, in order to fully apprehend the effects of neurotrophic treatment of degenerating SGCs and in order to consider clinical application of neurotrophins, future research should focus (a) on characterizing the expression pattern of neurotrophins in the cochlea after deafening, (b) on more detailed characterization of functional and morphological changes of SGCs associated with both deafening and neurotrophic treatment and (c) on the possible self-supporting state of SGCs after cessation of short-term neurotrophic treatment.
螺旋神经节细胞（SGC）在毛细胞丧失后发生的退行性变可以通过给予外源性神经营养因子来预防。许多这些神经营养因子，特别是神经营养因子脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3），已被描述为参与了啮齿动物耳蜗的发育。虽然大多数神经营养因子的表达在成年期下降到无法检测的水平（只有 NT-3 仍然高度表达），但其各自的受体仍然存在于 SGC 中。事实上，关于神经营养因子在成熟耳蜗中的功能知之甚少。这种知识对于寻找工具来改善耳蜗植入后 SGC 的存活至关重要。在这篇综述中，我们将从神经营养因子信号转导的基本细胞机制的角度，批判性地评价神经营养因子治疗 SGC 的当前实验结果。我们的结论是，为了充分理解神经营养治疗退行性 SGC 的效果，并考虑神经营养因子的临床应用，未来的研究应该集中在以下几个方面：（a）描述失聪后耳蜗中神经营养因子的表达模式；（b）更详细地描述与失聪和神经营养治疗相关的 SGC 的功能和形态变化；（c）停止短期神经营养治疗后 SGC 可能的自我维持状态。
