Structural changes in the inner ear over time studied in the experimentally deafened guinea pig

Abstract

Today a cochlear implant (CI) may significantly restore auditory function, even for people with a profound hearing loss. Because the efficacy of a CI is believed to depend mainly on the remaining population of spiral ganglion neurons (SGNs), it is important to understand the timeline of the degenerative process of the auditory neurons following deafness. Guinea pigs were transtympanically deafened with neomycin, verified by recording auditory brainstem responses (ABRs), and then sacrificed at different time points. Loss of SGNs as well as changes in cell body and nuclear volume were estimated. To study the effect of delayed treatment, a group of animals that had been deaf for 12 weeks was implanted with a stimulus electrode mimicking a CI, after which they received a 4-week treatment with glial cell-derived neurotrophic factor (GDNF). The electrical responsiveness of the SGNs was measured by recording electrically evoked ABRs. There was a rapid degeneration during the first 7 weeks, shown as a significant reduction of the SGN population. The degenerative process then slowed, and there was no difference in the amount of remaining neurons between weeks 7 and 18.

The feasibility of an encapsulated cell approach in an animal deafness model

“…Using an implanted stimulus electrode, eABRs could be measured for several weeks. The present study used three-week deafened guinea pigs that already had a 40% SGN loss [6] , [30] . The functional impairment was confirmed using ABR recordings prior to implantation of the CI in order to avoid any significant differences between the experimental groups.…”

“…It is well known that the SGN soma size changes after deafening, but the dynamics of these size changes are not clear. The results from measurements of SGN soma area vary between different laboratories [6] , [10] , [30] , [32] , [33] , [34] . This depends in part on using different techniques for measurements, deafening, and treatment, and not least for how long the animals have been deaf.…”

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

“…The dynamic of tissue reaction and degeneration of neural structures following cochlear implantation or other trauma may differ between rodents used in experimental hearing research and human beings. For example, in rodents a fast degeneration of spiral ganglia after loss of hair cells is seen within only a few weeks (17,(68)(69)(70)(71). This seems not to be the case in human patients (12)(13)(14)(15), in whom possible rehabilitation of hearing with the cochlear implant has been demonstrated even after years of deafness.…”

Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

“…In animal models, loss of cochlear hair cells associated reduction in neurotrophin production, causes atrophy of the peripheral spiral ganglion neurites in the osseous spiral lamina and subsequent progressive death of the neurons over periods of weeks to months (Fransson et al, 2017). Fortunately the human cochlea exhibits considerable resilience, with retention of much of the spiral ganglion neuron population for decades following loss of the hair cells (Leake et al, 1991;Nadol, 1997).…”