Does electrical stimulation of deaf cochleae prevent spiral ganglion degeneration?

Li, Li; Parkins, Charles W.; Webster, Douglas B.

doi:10.1016/s0378-5955(99)00043-x

Cited by 52 publications

(48 citation statements)

References 21 publications

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“…There was no significant effect of chronic ES alone on SGN survival, a finding consistent with previous studies in the cat [27,31,32] and guinea pig [8,33,34], although this is not a uniform finding [25,[35][36][37][38][39][40][41]. Differences in the methodology (e.g., the duration and severity of deafness, the age at deafness onset, electrode design and position, duration, and mode of chronic ES) complicate direct The mean (± SEM) of peripheral process packing density expressed as a percentage of the OSL.…”

Section: Effects Of Chronic Es On Sgn Survivalsupporting

confidence: 91%

Combining Cell-Based Therapies and Neural Prostheses to Promote Neural Survival

et al. 2011

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Cochlear implants provide partial restoration of hearing for profoundly deaf patients by electrically stimulating spiral ganglion neurons (SGNs); however, these neurons gradually degenerate following the onset of deafness. Although the exogenous application of neurotrophins (NTs) can prevent SGN loss, current techniques to administer NTs for long periods of time have limited clinical applicability. We have used encapsulated choroid plexus cells (NTCells; Living Cell Technologies, Auckland, New Zealand) to provide NTs in a clinically viable manner that can be combined with a cochlear implant. Neonatal cats were deafened and unilaterally implanted with NTCells and a cochlear implant. Animals received chronic electrical stimulation (ES) alone, NTs alone, or combined NTs and ES (ES + NT) for a period of as much as 8 months. The opposite ear served as a deafened unimplanted control. Chronic ES alone did not result in increased survival of SGNs or their peripheral processes. NT treatment alone resulted in greater SGN survival restricted to the upper basal cochlear region and an increased density of SGN peripheral processes. Importantly, chronic ES in combination with NTs provided significant SGN survival throughout a wider extent of the cochlea, in addition to an increased peripheral process density. Re-sprouting peripheral processes were observed in the scala media and scala tympani, raising the possibility of direct contact between peripheral processes and a cochlear implant electrode array. We conclude that cell-based therapy is clinically viable and effective in promoting SGN survival for extended durations of cochlear implant use. These findings have important implications for the safe delivery of therapeutic drugs to the cochlea.

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Section: Effects Of Chronic Es On Sgn Survivalsupporting

confidence: 91%

Combining Cell-Based Therapies and Neural Prostheses to Promote Neural Survival

et al. 2011

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“…Using a variety of animal models, a number of studies have demonstrated rescue effects associated with ES (Hartshorn et al, 1991;Kanzaki et al, 2002;Leake et al, 1999;Leake et al, 1991;Leake et al, 1992;Leake et al, 1995;Lousteau, 1987;Miller et al, 1995;Mitchell et al, 1997). In contrast, other studies report no trophic effects associated with ES per se (Araki et al, 1998;Coco et al, 2006;Li et al, 1999;Shepherd et al, 1994;Shepherd et al, 2005;Widijaja et al, 2006); these findings are consistent with a recent temporal bone study of 11 cochlear implant patients that showed no evidence of enhanced SGN survival in the implanted ear compared to the contralateral deafened control ear (Khan et al, 2005).…”

Section: Introductionmentioning

confidence: 54%

Neurotrophins and electrical stimulation for protection and repair of spiral ganglion neurons following sensorineural hearing loss

2008

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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.

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“…Although depolarization has been shown to provide a trophic influence on early postnatal SGNs in vitro (Hegarty et al, 1997;Hansen et al, 2001), chronic electrical stimulation (ES) of SGNs in ototoxically deafened animals has not consistently demonstrated that depolarization rescues SGNs in vivo. Several studies have reported an increase in SGN survival in deafened, chronically stimulated cochleae (Lousteau, 1987;Hartshorn et al, 1991;Hultcrantz et al, 1991;Leake et al, 1992;Leake et al, 1995;Mitchell et al, 1997;Leake et al, 1999), however other studies -including those from our laboratory -have shown no evidence of stimulus-induced trophic support of SGNs (Shepherd et al, 1994;Araki et al, 1998;Li et al, 1999;Shepherd et al, 2005).…”

Section: Introductionmentioning

confidence: 59%

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

et al. 2007

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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.

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Does electrical stimulation of deaf cochleae prevent spiral ganglion degeneration?

Cited by 52 publications

References 21 publications

Combining Cell-Based Therapies and Neural Prostheses to Promote Neural Survival

Combining Cell-Based Therapies and Neural Prostheses to Promote Neural Survival

Neurotrophins and electrical stimulation for protection and repair of spiral ganglion neurons following sensorineural hearing loss

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

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