Aanalysis of pathophysiogy of cochlear nerve degeneration based on quantifiable animal experimental model of cochlear nerve degeneration

虽然长期以来，耳蜗神经变性导致的听力损失一直被认为是一种不可逆转的过程，目前还没有可行的治疗方法，但最近的分子实验研究，如神经营养因子基因治疗的试验，逐渐使这种观点过时。在用于这类研究的活体模型中，耳蜗神经的外周(毛细胞侧)突起损伤导致耳蜗神经变性，但还没有可靠的实验模型表明耳蜗神经从中枢(脑干侧)突起开始变性。我们首先建立了一个中枢突起损伤模型，在该模型中可以定量评估耳蜗神经退行性变。利用该模型，我们观察了脑源性神经营养因子(BDNF)和神经营养素3(NT3)对耳蜗神经损伤的治疗作用。到目前为止，我们还没有检测到这些因素对预防耳蜗神经退变的任何效果。这些结果与体外实验的结果不同。这种差异可能至少部分源于损伤部位的不同，即外周突起或中央突起。有了中枢突起损伤模型，耳蜗神经变性的研究工具首次完善，因为耳蜗神经变性不仅可以从外周而且从中央侧进行彻底的研究。我们的实验模型可能会给我们提供仅通过外周突起损伤模型无法获得的知识。这可能成为未来控制良好的耳蜗神经病理科学研究的一项基础和有用的技术。

Although loss of hearing due to cochlear nerve degeneration has long been regarded as a sort of irreversible process to which no feasible measures have been available, recent molecular experimental studies such as the trials of neurotrophins gene therapy gradually make such view obsolete. In in vivo models used for such investigations, the peripheral (hair-cell side) process of the cochlear nerve is injured to induce cochlear nerve degeneration, but there has been no dependable experimental model in which cochlear nerve degeneration begins from the central (brainstem side) process. We first developed a central process injured model in which cochlear nerve degeneration resulted can be quantitatively evaluated. Using this model, we investigated the efficacy of various neurothophins, such as brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) on injured cochlear nerve. So far we have not detected any effects of these factors to prevent cochlear nerve degeneration. These results are different from those from in vitro experiments. Such difference may be derived at least partly from the difference of injury sites, namely peripheral process or central process. Having a central process injured model, the tools to investigate cochlear nerve degeneration are first completed because cochlear nerve degeneration could be thoroughly investigated not only from the peripheral but also from the central side. Our experimental model may give us the knowledge that could not obtain only by the peripheral process injured models. This may become a basic and useful technique for well-controlled scientific research on cochlear nerve pathologies in the future.