Does cochlear implantation and electrical stimulation affect residual hair cells and spiral ganglion neurons?

Abstract

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.

Figure 1

X-ray image of a cat cochlea showing the electrode array within the scala tympani. The helical platinum-iridium leadwire system is connected to a stainless steel leadwire system at the connector which is located within the animal's bulla. The stainless steel leadwire exits the skin at the nape of the neck and is directly connected to a portable programmable stimulator worn in a back pack (not illustrated). Electrodes are numbered 1-8 (apical to basal); round window niche; RWN. Scale bar = 1 mm

Figure 2

1. A and B: Representative examples of click-evoked ABRs recorded prior to implantation (A) and at the end of ES, 195 days post implant surgery (B; I6_p). T= denotes threshold.

2. C: Normalized ABR thresholds as a function of implantation time for ES (●) and non-stimulated (○) cochleae of partially deaf animals (n= 4; mean ± sem). Click thresholds exhibited a statistically significant reduction as a function of implantation time. This reduction was not influenced by chronic ES.

3. D: CAP thresholds recorded from the stimulated cochleae as a function of implantation time: 0.5 KHz ●; 1.0 KHz▼; 2.0 KHz■ ; 4.0 KHz◆. (n= 4; normalized mean ± sem). CAP thresholds showed no significant change over time.

Figure 3

1. A & B: Representative EABRs recorded post operatively (A) and at the completion of ES, 195 days later (B; I5_s). T= threshold.

2. C: Change in EABR threshold normalized to the first post-operative response as a function of implant time (n=6; mean ± sem; * = p<0.05).

3. D: Change in the gradient of the normalized input-output function (I/O) curve as a function of stimulation time (n=6; mean ± sem). ● Recorded from apical electrodes of broad ES group: (electrodes 1-3); ○ Recorded from basal electrodes of broad ES group (electrodes 6-8); ▼Recorded from apical electrodes of narrow ES group (electrodes 1-3); ▽ Recorded from basal electrodes of narrow ES group (electrodes 6-8).

4. E (I4p) & F (I5s): Two representative EABR I/O functions plotted periodically over the course of their chronic stimulation program. Open symbols are used to identify the first and last I/O recordings for each animal.

○ 2 weeks ; ■ 6 weeks; ▲10 weeks; ● 14 weeks; ▶18 weeks; ▼ 22 weeks; ◀ 26 weeks; ◆ 30 weeks; ◢ 34 weeks; □ 36 weeks post implantation

Figure 4

Representative photomicrographs illustrating a low power of each cochlear turn and a higher power photomicrograph of the adjacent Rosenthal's canal from the ES (a-c; left panel) and non-stimulated cochleae (d-f; right panel) of a severely deafened animal (I1s). The cochleae in this example were implanted for a period of 252 days and the left cochlea received in excess of 1000 h of ES. Apical turn 4a and 4d; middle turn 4b and 4e; basal turn 4c and 4f. Scale bar: low power=100μm; high power=20μm.

Figure 5

Representative photomicrographs illustrating a low power of each cochlear turn and a higher power photomicrograph of the adjacent Rosenthal's canal from the ES (a-c; left panel) and non-stimulated cochleae (d-f; right panel) of a partially deafened animal (I7p). The cochleae in this example were implanted for a period of 207 days and the left cochlea received 900 h of ES. Apical turn 5a and 5d; middle turn 5b and 5e; basal turn 5c and 5f. Scale bar: low power=100μm; high power=20μm.

Figure 6

Mean (± sem) hair cell survival in the partial hearing group expressed as a percentage hair cell survival. ■ non-stimulated (n=4 cochleae); □ ES (n=4).

Figure 7

A. Mean SGN density for the basal, middle and apical turns of the ■ non-stimulated (n=4 cochleae) and □ ES (n=4) of the severely deaf group. B. Mean SGN density for the basal, middle and apical turns of ■ non-stimulated (n=4) and □ ES (n=4) of the partial hearing group (mean ± sem).

Figure 8

A. Mean SGN soma area in the basal, middle and apical turns of the ■ non-stimulated (n=4 cochleae) and □ ES (n=4) of the severely deaf group. B. Mean SGN soma area in basal, middle and apical turns of the ■ non-stimulated control (n=4) and □ ES (n=4) of the partial hearing group (mean ± sem).