After substantial loss of cochlear hair cells, exogenous
neurotrophins prevent degeneration of the auditory nerve. Because
cochlear implantation, the current
therapy for profound
sensorineural hearing loss, depends on a functional nerve, application of
neurotrophins is being investigated. We addressed two questions important for fundamental insight into the effects of exogenous
neurotrophins on a degenerating neural system, and for translation to the clinic. First, does temporary treatment with
brain-derived neurotrophic factor (
BDNF) prevent
nerve degeneration on the long term? Second, how does a
BDNF-treated nerve respond to electrical stimulation? Deafened guinea pigs received a
cochlear implant, and their cochleas were infused with
BDNF for 4 weeks. Up to 8 weeks
after treatment, their cochleas were analyzed histologically. Electrically evoked compound action potentials (eCAPs) were recorded using stimulation paradigms that are informative of neural survival. Spiral ganglion cell (SGC) degeneration was prevented during
BDNF treatment, resulting in 1.9 times more SGCs than in deafened untreated cochleas. Importantly, SGC survival was almost complete 8 weeks
after treatment cessation, when 2.6 times more SGCs were observed. In four eCAP characteristics (three involving alteration of the interphase gap of the biphasic current pulse and one involving pulse trains), we found large and statistically significant differences between normal-hearing and deaf controls. Importantly, for
BDNF-treated animals, these eCAP characteristics were near normal, suggesting healthy responsiveness of
BDNF-treated SGCs. In conclusion, clinically practicable short-term
neurotrophin treatment is sufficient for long-term survival of SGCs, and it can restore or preserve SGC function well beyond the treatment period. Significance statement: Successful restoration of hearing in deaf subjects by means of a
cochlear implant requires a healthy spiral ganglion cell population.
Deafness-induced degeneration of these cells can be averted with
neurotrophic factors. In the present study in deafened guinea pigs, we investigated the long-term effects of temporary (i.e., clinically practicable) treatment with
brain-derived neurotrophic factor (
BDNF). We show that,
after treatment cessation, the
neuroprotective effect remains for at least 8 weeks. Moreover, for the first time, it is shown that the electrical responsiveness of
BDNF-treated spiral ganglion cells is preserved during this period as well. These findings demonstrate that treatment of the auditory nerve with
neurotrophic factors may be relevant for
cochlear implant users.