Glial cell line-derived neurotrophic factor and antioxidants preserve the electrical responsiveness of the spiral ganglion neurons after experimentally induced deafness

• Published in: Neurobiology of disease Vol. 29; no. 1; pp. 14 - 21
• Main Authors: Maruyama, Jun, Miller, Josef M, Ulfendahl, Mats
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2008; Elsevier
• Subjects: Acoustic Stimulation - methods; Animals; Antioxidants; Antioxidants - pharmacology; Ascorbic Acid - pharmacology; Auditory brainstem response; Auditory Threshold - drug effects; Auditory Threshold - physiology; Auditory Threshold - radiation effects; Chromans - pharmacology; Cochlea; Deafferentation; Deafness - pathology; Disease Models, Animal; Dose-Response Relationship, Radiation; Drug Administration Routes; Electric Stimulation - methods; Electrical; Evoked Potentials, Auditory, Brain Stem - drug effects; Evoked Potentials, Auditory, Brain Stem - physiology; Evoked Potentials, Auditory, Brain Stem - radiation effects; GDNF; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Guinea Pigs; Inner ear; Intervention; Medicin och hälsovetenskap; Neurology; Neurons - drug effects; Neurons - radiation effects; Neurotrophic factor; Spiral ganglion; Spiral Ganglion - pathology; Statistics, Nonparametric; Antioxidants; Intervention; Spiral ganglion; Neurotrophic factor; Auditory brainstem response; GDNF; Cochlea; Electrical; Deafferentation; Inner ear
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2007.07.026

Abstract Cochlear implant surgery is currently the therapy of choice for profoundly deaf patients. However, the functionality of cochlear implants depends on the integrity of the auditory spiral ganglion neurons. This study assesses the combined efficacy of two classes of agents found effective in preventing degeneration of the auditory nerve following deafness, neurotrophic factors, and antioxidants. Guinea pigs were deafened and treated for 4 weeks with either local administration of GDNF or a combination of GDNF and systemic injections of the antioxidants ascorbic acid and Trolox. The density of surviving spiral ganglion cells was significantly enhanced and the thresholds for eliciting an electrically evoked brain stem response were significantly reduced in GDNF treated animals compared to deafened-untreated. The addition of antioxidants significantly enhanced the evoked responsiveness over that observed with GDNF alone. The results suggest multiple sites of intervention in the rescue of these cells from deafferentation-induced cell death.