title: Therapeutic effect of adeno-associated virus (AAV)-mediated ADNF-9 expression on cochlea of kanamycin-deafened guinea pigs.
abstract: CONCLUSIONS
  rAAV-NT4-ADNF-9 could ameliorate the damage to auditory function and repair previous impairment of cochlear hair cell loss induced by kanamycin.
  
  
  OBJECTIVE
  To investigate the therapeutic effect of ADNF-9 on cochlear hair cells using the recombinant adeno-associated virus (AAV) carrying fusion gene NT4-ADNF-9 and the kanamycin-deafened guinea pig model.
  
  
  METHODS
  Forty white guinea pigs with normal auricle reflex and normal auditory brainstem responses (ABRs) were randomly divided into four groups. Kanamycin was administered to the animals in groups A, B, and C to establish the deafened guinea pig model. rAAV-NT4-ADNF-9, vector only, and artificial perilymph were then delivered to the cochlear tissue of animals in groups A, B, and C, respectively, through the round window membrane. Animals in group D did not receive any treatment and acted as normal controls. The hearing thresholds on the surgery side were recorded before and after the transfection treatment. Fourteen days after treatment, cochleae were removed for paraffin slide preparation and cochlear surface preparation. A phase contrast microscope was used to observe the protective effect of ADNF-9 on hair cells.
  
  
  RESULTS
  Significant reduction of the ABR threshold was observed after rAAV-NT4-ADNF-9 treatment (p < 0.05). After 14 days of treatment, the ABR threshold was also significantly different between the rAAV-NT4-ADNF-9-infected group and the non-infected group. Moreover, phase contrast microscopy showed significantly less hair cell damage or hair cell loss in the group treated with rAAV-NT4-ADNF-9 than in the groups treated with vector only or artificial perilymph (p < 0.05).
authors.affiliation: Department of Otorhinolaryngology, Second Hospital of Xi`an jiaotong University , Xi`an.
authors.forename: Guoxi
authors.initials: G
authors.lastname: Zheng
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Kang
authors.initials: K
authors.lastname: Zhu
authors.forename: Junrong
authors.initials: J
authors.lastname: Wei
authors.forename: Yang
authors.initials: Y
authors.lastname: Jing
authors.forename: Maoli
authors.initials: M
authors.lastname: Duan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology; D003638:Deafness / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005822:Genetic Vectors; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism; D007612:Kanamycin / Q000633:toxicity; D009842:Oligopeptides / Q000096:biosynthesis*; D014162:Transfection
chemical_list: D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; D007612:Kanamycin