Effects of ototoxic deafening and chronic stimulation on auditory-nerve survival and electrical hearing in guinea pigs.

摘要

Cochlear implant performance is believed to depend in part on the state of the auditory nerve array. Following deafening, the auditory nerve undergoes progressive degenerative changes, including loss of spiral ganglion cells (SGCs) and changes in cell size and myelination. If loss of SGCs is a primary determinant of function, then SGC protection should enhance implant function. Electrical stimulation has been shown to protect SGC. To better characterize the impact of SGC survival on implant performance, we examined the relationship between electrical detection threshold level and SGC survival (presence) in individual animals, and as a function of time (comparing across animals) using psychophysically-trained, ototoxically-deafened guinea pigs. Surprisingly, while both threshold level and SGC survival changed as a function of time post-deafening, they did not follow comparable time courses. Early changes in threshold level preceded significant changes in SGC survival, and periods of rapid SGC loss occurred when threshold levels were stable. In long-deafened animals, for which both threshold level and SGC survival were relatively stable, thresholds at short phase durations were correlated with survival. In general, however, large differences in SGC survival were associated with relatively small threshold differences. Furthermore, despite significant enhancement of SGC survival with chronic stimulation, thresholds for stimulated and unstimulated animals were indistinguishable. These results suggest that stimulus detection is relatively insensitive to auditory nerve changes. However, they could also reflect the insensitivity of cell counts and densities to the physiological responsiveness of the auditory nerve (i.e., cell survival may not be linearly related to nerve function) and/or confounding effects of central auditory changes that affect stimulus detection.; The SGC enhancement in stimulated ears was similar by SGC count and density assessment. Furthermore, by chronically infusing verapamil into the inner ear of chronically stimulated and unstimulated animals, we were able to reduce the protective efficacy of chronic stimulation without altering the evoked response. Taken together, these results suggest that the observed changes are not stimulation-induced artifacts of alterations in the dimensions of the canal within which the ganglion is located, but rather, are true neuroprotective effects.