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Exogenous neurotrophins (NTs) have been shown to rescue spiral ganglion neurons (SGNs) from degeneration following a sensorineural hearing loss (SNHL). Furthermore, chronic electrical stimulation (ES) has been shown to retard SGN degeneration in some studies but not others. Since there is evidence of even greater SGN rescue when NT administration is combined with ES, we examined whether chronic ES can maintain SGN survival long after cessation of NT delivery. Young adult guinea pigs were profoundly deafened using ototoxic drugs; five days later they were unilaterally implanted with an electrode array and drug delivery system. Brain derived neurotrophic factor (BDNF) was continuously delivered to the scala tympani over a four week period while the animal simultaneously received ES via bipolar electrodes in the basal turn (i.e., turn 1) scala tympani. One cohort (n=5) received ES for six weeks (i.e., including a two week period after the cessation of BDNF delivery; ES(6)); a second cohort (n=5) received ES for 10 weeks (i.e., a six week period following cessation of BDNF delivery; ES(10)). The cochleae were harvested for histology and SGN density determined for each cochlear turn for comparison with normal hearing controls (n=4). The withdrawal of BDNF resulted in a rapid loss of SGNs in turns 2-4 of the deafened/BDNF-treated cochleae; this was significant as early as two weeks following removal of the NT when compared with normal controls (p<0.05). Importantly, there was not a significant reduction in SGNs in turn 1 (i.e., adjacent to the electrode array) two and six weeks after NT removal, as compared with normal controls. This result suggests that chronic ES can prevent the rapid loss of SGNs that occurs after the withdrawal of exogenous NTs. Implications for the clinical delivery of NTs are discussed.

Increasing numbers of cochlear implant subjects have some level of residual hearing at the time of implantation. The present study examined whether (i) hair cells that have survived one pathological insult (aminoglycoside deafening), can survive and function following long-term cochlear implantation and electrical stimulation (ES); and (ii) chronic ES in these cochleae results in greater trophic support of spiral ganglion neurons (SGNs) compared with cochleae devoid of hair cells. Eight cats, with either partial (n=4) or severe (n=4) sensorineural hearing loss, were bilaterally implanted with scala tympani electrode arrays 2 months after deafening, and received unilateral ES using charge balanced biphasic current pulses for periods of up to 235 days. Frequency-specific compound action potentials and click-evoked auditory brainstem responses (ABRs) were recorded periodically to monitor the residual acoustic hearing. Electrically evoked ABRs (EABRs) were recorded to confirm the stimulus levels were 3-6 dB above the EABR threshold. On completion of the ES program the cochleae were examined histologically. Partially deafened animals showed no significant increase in acoustic thresholds over the implantation period. Moreover, chronic ES of an electrode array located in the base of the cochlea did not adversely affect hair cells in the middle or apical turns. There was evidence of a small but statistically significant rescue of SGNs in the middle and apical turns of stimulated cochleae in animals with partial hearing. Chronic ES did not, however, prevent a reduction in SGN density for the severely deaf cohort, although SGNs adjacent to the stimulating electrodes did exhibit a significant increase in soma area (p<0.01). In sum, chronic ES in partial hearing animals does not adversely affect functioning residual hair cells apical to the electrode array. Moreover, while there is an increase in the soma area of SGNs close to the stimulating electrodes in severely deaf cochleae, this trophic effect does not result in increased SGN survival.