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

虽然耳蜗神经变性导致的听力损失一直被认为是一种不可逆的过程，没有可行的措施，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。在用于这种研究的体内模型中，耳蜗神经的外周（毛细胞侧）突起被损伤以诱导耳蜗神经变性，但是还没有可靠的实验模型，其中耳蜗神经变性从中枢（脑干侧）突起开始。我们首先建立了一个中枢神经损伤模型，其中所导致的耳蜗神经变性可以定量评估。利用这个模型，我们研究了各种神经营养素，如脑源性神经营养因子（BDNF）和神经营养素3（NT 3）对损伤的耳蜗神经的疗效。到目前为止，我们还没有发现这些因素对防止耳蜗神经变性的任何影响。这些结果与体外实验结果不同。这种差异可能至少部分来源于损伤部位的差异，即外周突或中央突。由于耳蜗神经变性不仅可以从外周侧观察，而且可以从中枢侧观察，因此，通过建立中枢突损伤模型，首先完善了研究耳蜗神经变性的工具。我们的实验模型可能会给我们提供一些仅通过周围突损伤模型无法获得的知识。这可能成为一个基本的和有用的技术，为良好的控制科学研究的耳蜗神经病理学在未来。

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.