Dodson H C
Institute of Laryngology and Otology, University College London, UK.
J Neurocytol. 1997 Aug;26(8):541-56. doi: 10.1023/a:1015434524040.
Loss of cochlear hair cells results in a loss of ganglion cells and further neurodegenerative changes throughout the auditory pathway. Understanding more about the early stages of ganglion cell loss in vivo may lead to ways of ameliorating or preventing the loss of these neurons. To examine these stages, the effects of intracochlear perfusion with aminoglycoside antibiotics on the organ of Corti and spiral ganglion cells were evaluated in young adult guinea pigs at survival periods ranging from 1 hour to 12 weeks, using immunocytochemical and ultrastructural techniques. At 1 hour survival a base-to-apex gradient of damage was indicated in the cochlea by the appearance of severely damaged hair cells and injured ganglion cells in the basal coil while in the apical coil, hair cells were damaged but intact and ganglion cells appeared normal. By 4 hours the appearance of severely disrupted hair cells and damaged ganglion cells had extended throughout the cochlea. The ultrastructural appearance of many injured ganglion cells demonstrated features characteristic of cell death including condensed cytoplasm, non-marginal clumping of nuclear chromatin, and wrinkled nuclear membrane. Despite the loss of many ganglion cells, a population of these cells remained at 12 weeks survival. These contained large amounts of rough endoplasmic reticulum, were unmyelinated apart from the central process and were surrounded by satellite cells. These features are typical of ganglion cells during development, before the onset of hearing. Immunolabelling of cochlear whole mounts after hair cell destruction with protein gene product 9.5 (PGP 9.5) revealed the presence of neural elements in the organ of Corti at up to 12 weeks survival. These may be associated with the remaining ganglion cells. In these surviving ganglion cells, the intense labelling with PGP 9.5 together with the increase in rough endoplasmic reticulum, indicates the presence of active protein synthesis which may be connected with their survival.
耳蜗毛细胞的丧失会导致神经节细胞的丧失，并在整个听觉通路中引发进一步的神经退行性变化。更深入地了解体内神经节细胞丧失的早期阶段，可能会找到改善或预防这些神经元丧失的方法。为了研究这些阶段，我们使用免疫细胞化学和超微结构技术，在存活时间从1小时到12周不等的成年豚鼠中，评估了耳蜗内灌注氨基糖苷类抗生素对柯蒂氏器和螺旋神经节细胞的影响。在存活1小时时，耳蜗底部至顶部出现损伤梯度，表现为基底回中严重受损的毛细胞和受损的神经节细胞，而在顶回中，毛细胞虽有损伤但仍完整，神经节细胞看起来正常。到4小时时，严重受损的毛细胞和受损的神经节细胞已遍布整个耳蜗。许多受损神经节细胞的超微结构特征显示出细胞死亡的特征，包括细胞质浓缩、核染色质非边缘性聚集以及核膜皱缩。尽管许多神经节细胞丧失，但仍有一部分细胞在存活12周时留存下来。这些细胞含有大量粗面内质网，除中央突外无髓鞘，且被卫星细胞包围。这些特征是发育过程中、听力开始之前神经节细胞的典型特征。用蛋白质基因产物9.5（PGP 9.5）破坏毛细胞后对耳蜗整装标本进行免疫标记，结果显示在存活长达12周的柯蒂氏器中存在神经成分。这些可能与剩余的神经节细胞有关。在这些存活的神经节细胞中，PGP 9.5的强烈标记以及粗面内质网的增加，表明存在活跃的蛋白质合成，这可能与其存活有关。
