Dodson H C, Mohuiddin A
Institute of Laryngology and Otology, University College London, 330/335 Gray's Inn Road, London WC1X 8EE, UK.
J Neurocytol. 2000 Jul;29(7):525-37. doi: 10.1023/a:1007201913730.
Loss of ganglion cells after hair cell destruction in the mammalian cochlea continues to occur over a long period of time, with the possibility of more than one factor contributing to this process. Despite the absence of hair cells, some ganglion cells are, however, able to survive for considerable periods of time. Because functional ganglion cells are crucial to the successful use of cochlear implants, a better understanding of the response of these cells to injury is required so that their loss can be prevented or ameliorated. Quantitative light microscopy, electron microscopy and immunocytochemical techniques were used to examine the response of type I spiral ganglion neurones to hair cell destruction, in guinea pigs at 1, 3, 6 and 30 weeks survival following intracochlear injection with gentamicin. The time course of ganglion cell loss was determined, while a closer examination of those cells able to survive was carried out. A significant early loss of large numbers of ganglion cells was followed by a further significant loss of these cells by 30-week survival. At the same time a decrease in the numbers of central fibres was also observed. Surviving ganglion cells have little or no perikaryal myelin, an appearance resembling that of type I ganglion cells at 55 days gestation. Ganglion cells surviving the initial loss were also found to have a significantly larger soma size than controls although this was not maintained and at 30 weeks survival the few remaining cells were similar in size to that of controls. The growth associated protein GAP 43 was upregulated in surviving ganglion cells at 3 weeks survival, but appeared diminished by 6 weeks survival. These features may indicate a survival response in ganglion cells and may provide a basis on which to develop appropriate means to prevent their loss.
在哺乳动物耳蜗中,毛细胞破坏后神经节细胞的损失会在很长一段时间内持续发生,这一过程可能由多种因素导致。尽管没有毛细胞,但仍有一些神经节细胞能够存活相当长的时间。由于功能性神经节细胞对于成功使用人工耳蜗至关重要,因此需要更好地了解这些细胞对损伤的反应,以便预防或减轻它们的损失。采用定量光学显微镜、电子显微镜和免疫细胞化学技术,研究了豚鼠在耳蜗内注射庆大霉素后1周、3周、6周和30周存活时,I型螺旋神经节神经元对毛细胞破坏的反应。确定了神经节细胞损失的时间进程,同时对那些能够存活的细胞进行了更仔细的检查。大量神经节细胞在早期显著损失,到30周存活时这些细胞进一步显著损失。与此同时,还观察到中枢纤维数量减少。存活的神经节细胞几乎没有或没有核周髓磷脂,这种外观类似于妊娠55天时的I型神经节细胞。在最初的损失中存活下来的神经节细胞的胞体大小也明显大于对照组,尽管这种情况并没有持续下去,到30周存活时,剩下的少数细胞大小与对照组相似。生长相关蛋白GAP 43在存活3周的神经节细胞中上调,但在存活6周时似乎减少。这些特征可能表明神经节细胞的存活反应,并可能为开发预防其损失的适当方法提供基础。