An in vivo quantifiable model of cochlear neuronal degeneration induced by central process injury.

在现有的耳蜗神经元变性的体内实验模型中，耳蜗神经的外周（毛细胞侧）突被损伤以诱导神经元变性。然而，目前还没有可靠的实验模型表明耳蜗神经元变性是从中枢（脑干侧）过程开始的。缺乏中枢过程损伤模型可能是由于必须克服实验上的困难，以便在小实验动物（如大鼠）中可重复和选择性地损伤耳蜗神经元的中枢过程，同时保持内听动脉的通畅。利用大鼠，我们首先建立了一个中央过程损伤模型，其中螺旋神经节细胞因耳蜗神经元逆行变性而减少可以定量评估。在我们的实验模型中，耳蜗神经被放置在内耳道的压迫记录（CR）电极压迫和损伤。首先将耳蜗神经压缩至耳蜗神经复合动作电位变平，然后以不同的压缩速度（5、10、200 μm /sec）将CR电极推进至相同深度（400μm）。因此，在我们的模型中，螺旋神经节细胞的减少是由压缩速度引起的。这种方法可以对耳蜗神经造成压迫性损伤，而没有证据表明耳蜗经内听动脉的血液供应受到损害。该模型为我们提供了获取知识的手段，这是以前不可能从外周过程损伤模型中得出的。

In the available in vivo experimental models for cochlear neuronal degeneration, the peripheral (hair-cell side) process of the cochlear nerve has been injured in order to induce neuronal degeneration. However, there has been no dependable experimental model in which cochlear neuronal degeneration begins from the central (brainstem side) process. This lack of a central process injury model has probably been due to the experimental difficulties that had to be overcome in order to reproducibly and selectively injure the central process of the cochlear neurons while maintaining the patency of the internal auditory artery in small experimental animals such as rats. Using rats, we first developed a central process injury model in which the reduction of the spiral ganglion cells due to retrograde degeneration of cochlear neurons can be quantitativery evaluated. In our experimental model, the cochlear nerve was compressed and injured by a compression-recording (CR) electrode placed at the internal auditory meatus. First, the cochlear nerve was compressed until the compound action potentials of the cochlear nerve became flat, and then the CR electrode was advanced by various compression speeds (5, 10, or 200 μ m/sec) to reach the same depth (400μm). In our model, therefore, the reduction of the spiral ganglion cells was caused compression-speed-dependently. This method made it possible to produce compression injury to the cochlear nerve without evidence of damage to the blood supply to the cochlea via the internal auditory artery. This model gives us the means to obtain knowledge that was previously impossible to derive from the peripheral process injury models.