Effects of antioxidants on auditory nerve function and survival in deafened guinea pigs

• Published in: Neurobiology of disease Vol. 25; no. 2; pp. 309 - 318
• Main Authors: Maruyama, Jun, Yamagata, Takahiko, Ulfendahl, Mats, Bredberg, Göran, Altschuler, Richard A, Miller, Josef M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2007; Elsevier
• Subjects: Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Ascorbic acid; Ascorbic Acid - pharmacology; Auditory Threshold - drug effects; Auditory Threshold - physiology; Cell Survival - drug effects; Cell Survival - physiology; Chromans - pharmacology; Cochlear Nerve - drug effects; Cochlear Nerve - metabolism; Cochlear Nerve - physiopathology; Deafferentation; Deafness - drug therapy; Deafness - metabolism; Deafness - physiopathology; Denervation; Electrical auditory brainstem response; Evoked Potentials, Auditory, Brain Stem - drug effects; Evoked Potentials, Auditory, Brain Stem - physiology; Guinea Pigs; Hair Cells, Auditory - injuries; Hair Cells, Auditory - physiopathology; Hearing Loss, Sensorineural - drug therapy; Hearing Loss, Sensorineural - metabolism; Hearing Loss, Sensorineural - physiopathology; Male; Medicin och hälsovetenskap; Neurology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Neurons, Afferent - pathology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidative Stress - drug effects; Oxidative Stress - physiology; Spiral Ganglion - drug effects; Spiral Ganglion - metabolism; Spiral Ganglion - physiopathology; Spiral ganglion cell; Treatment Outcome; Trolox; Vitamin C; Vitamin E; Ascorbic acid; Vitamin E; Trolox; Vitamin C; Electrical auditory brainstem response; Deafferentation; Spiral ganglion cell
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2006.09.012

Abstract Based on in vitro studies, it is hypothesized that neurotrophic factor deprivation following deafferentation elicits an oxidative state change in the deafferented neuron and the formation of free radicals that then signal cell death pathways. This pathway to cell death was tested in vivo by assessing the efficacy of antioxidants (AOs) to prevent degeneration of deafferented CNVIII spiral ganglion cells (SGCs) in deafened guinea pigs. Following destruction of sensory cells, guinea pigs were treated immediately with Trolox (a water soluble vitamin E analogue) + ascorbic acid (vitamin C) administered either locally, directly in the inner ear, or systemically. Electrical auditory brainstem response (EABR) thresholds were recorded to assess nerve function and showed a large increase following deafness. In treated animals EABR thresholds decreased and surviving SGCs were increased significantly compared to untreated animals. These results indicate that a change in oxidative state following deafferentation plays a role in nerve cell death and antioxidant therapy may rescue SGCs from deafferentation-induced degeneration.