Adenovirus-mediated expression of brain-derived neurotrophic factor protects spiral ganglion neurons from ototoxic damage.
Hair cell loss, the most common cause of deafness, is often associated with auditory nerve degeneration. Our goal was to determine the influence of combined ciliary-derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) gene therapy on the survival of spiral ganglion neurons (SGNs) after elimination of inner hair cells in the mature guinea pig ear. Seven days after bilateral deafening, a 5-microl suspension of CNTF and/or BDNF adenovirus vectors was injected into the left scala tympani through the round window. Animals were sacrificed 28 days after deafening, and their inner ears were prepared for SGN counts. The SGN counts revealed that BDNF alone and the combined CNTF and BDNF treatment significantly enhanced SGN survival. CNTF did not significantly enhance the protective effect of BDNF. These data present possible strategies for enhancing SGN survival in cochlear implant procedures.
Nakaizumi
Toshihiko
T
KHRI, University of Michigan, Ann Arbor, Mich. 48109-0648, USA.
Kawamoto
Kohei
K
Minoda
Ryosei
R
Raphael
Yehoash
Y
D000256:Adenoviridae; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000517:prevention & control*; D009410:Nerve Degeneration / Q000517:prevention & control*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor