title: Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss.
abstract: Following destruction of sensory cells of the organ of Corti, spiral ganglion cells (SGC) in the guinea pig degenerate. Chronic electrical stimulation via cochlear prostheses can enhance their survival, with the effect blocked by stopping the electrically elicited action potentials with tetrodotoxin. Blocking action potentials in the normal hearing ear with tetrodotoxin, however, does not cause degeneration. This suggests that in the pathological ear VIII N activity acts as a survival factor, while in the normal ear there are other survival factors that maintain SGCs. We examined neurotrophins, as survival factors in the deafened ear. Two weeks of treatment with BDNF (brain derived neurotrophic factor) administered chronically via a mini-osmotic pump into scala tympani at 50 ng/ml, provided a statistically significant enhanced SGC survival over untreated deafened ears or deafened ears treated with artificial perilymph. Neurotrophin 3 provided some enhanced survival, but this was not statistically significant over untreated deafened ears. These observations suggest there are survival factors in the inner ear, including those coupled to direct activation of the auditory nerve fibers, that may serve to maintain the auditory nerve. These factors may be applied following deafness to maintain and enhance neural populations and to increase benefits to the profoundly deaf receiving cochlear implants.
authors.affiliation: Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Miller
authors.forename: D H
authors.initials: DH
authors.lastname: Chi
authors.forename: L J
authors.initials: LJ
authors.lastname: O'Keeffe
authors.forename: P
authors.initials: P
authors.lastname: Kruszka
authors.forename: Y
authors.initials: Y
authors.lastname: Raphael
authors.forename: R A
authors.initials: RA
authors.lastname: Altschuler
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D000963:Antimetabolites / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003051:Cochlea / Q000166:cytology / Q000187:drug effects; D003638:Deafness / Q000139:chemically induced / Q000473:pathology; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000166:cytology* / Q000187:drug effects; D007612:Kanamycin / Q000633:toxicity; D009414:Nerve Growth Factors / Q000494:pharmacology*; D020933:Neurotrophin 3; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects; D017933:Peripheral Nervous System / Q000166:cytology / Q000187:drug effects; D013136:Spiral Ganglion / Q000166:cytology* / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000963:Antimetabolites; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D007612:Kanamycin