Topographic and quantitative evaluation of gentamicin-induced damage to peripheral innervation of mouse cochleae.
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.