title: Vector-mediated delivery of bcl-2 prevents degeneration of auditory hair cells and neurons after injury.
abstract: OBJECTIVE
  To test the hypothesis that bcl-2 prevents oxidative stress-induced apoptosis of auditory sensory cells in explants of the organ of Corti and dissociated cell cultures of the spiral ganglion.
  
  
  METHODS
  Organ of Corti explants and dissociated spiral ganglion cell cultures obtained from 3-day-old (P3) rats or adult spiral ganglion cell cultures from 28-day-old (P28) rats were transduced with vectors containing a human bcl-2 gene. Cultures were then exposed to neomycin, cisplatin or subjected to withdrawal of neurotrophin supplementation. Outcome measures included hair cell and neuron counts, mitochondrial membrane potential and a histological measure of apoptosis.
  
  
  RESULTS
  Expression of bcl-2 in the organ of Corti explants and neuronal cell cultures provided a significant level of protection against cell death. Bcl-2 expression in the organ of Corti explants also protected mitochondria from loss of membrane potential and blocked an early step in the commitment of hair cells to apoptosis.
  
  
  CONCLUSIONS
  Expression of bcl-2 in cochlear tissues protects sensory cells from a variety of insults that have been demonstrated to damage the inner ear.
authors.affiliation: Department of Otolaryngology, University of Kansas, Kansas City, Kans 66160, USA. hstaecker@kumc.edu
authors.forename: Hinrich
authors.initials: H
authors.lastname: Staecker
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Lefebvre
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Van De Water
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D019254:Genes, bcl-2 / Q000502:physiology*; D005822:Genetic Vectors; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D009355:Neomycin / Q000633:toxicity; D009410:Nerve Degeneration / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009355:Neomycin; D002945:Cisplatin