Glial cell line-derived neurotrophic factor and antioxidants preserve the electrical responsiveness of the spiral ganglion neurons after experimentally induced deafness.
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.
Maruyama
Jun
J
Center for Hearing and Communication Research, Karolinska Institutet, Sweden.
Miller
Josef M
JM
Ulfendahl
Mats
M
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002839:Chromans / Q000494:pharmacology*; D003638:Deafness / Q000473:pathology; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004333:Drug Administration Routes; D004558:Electric Stimulation / Q000379:methods*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D006168:Guinea Pigs; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects*; D013136:Spiral Ganglion / Q000473:pathology*; D018709:Statistics, Nonparametric
D000975:Antioxidants; D002839:Chromans; D051100:Glial Cell Line-Derived Neurotrophic Factor; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid