In vitro and in vivo assessment of the ability of adeno-associated virus - Brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult

Anil K. Lalwani, Jay J. Han, Caley M. Castelein, Gerard J. Carvalho, Anand N. Mhatre

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Objectives/Hypothesis: Auditory dysfunction following ototoxic insult results from loss of cochlear hair cells. Secondary degeneration of auditory neurons ensues from withdrawal of neurotrophic support from hair cells and can be prevented with administration of neurotrophins. Administration of adeno-associated virus containing the gene for brain-derived neurotrophic factor will promote spiral ganglion neuron survival after the destruction of hair cells. Methods: Prevention of aminoglycoside-induced spiral ganglion neuron loss through the expression of brain-derived neurotrophic factor mediated by means of the adeno-associated virus was tested in vitro in cochlear explants and in vivo in mammalian cochlea. Results: Neuronal survival was significantly enhanced in adeno-associated virus-brain-derived neurotrophic factor transfected rat cochlear explants compared with control samples (30% vs. 19%, P <.05) following exposure to aminoglycoside. Following deafening with aminoglycoside and loop diuretic and introduction of adeno-associated virus-brain-derived neurotrophic factor through osmotic minipump, the experimental group of animals infused with adeno-associated virus-brain-derived neurotrophic factor displayed enhanced spiral ganglion neuron survival in the basal turn of the cochlea when compared with the control group infused with adeno-associated virus containing green fluorescent protein reporter gene. Conclusions: Administration of adeno-associated virus-brain-derived neurotrophic factor enhances spiral ganglion neuron survival following ototoxic exposure in vitro and in vivo. These studies lay the groundwork for further exploration of its application as an adjunct therapy for patients undergoing cochlear implantation because the success of implantation depends directly on the population of neurons available for electrical stimulation.

Original languageEnglish (US)
Pages (from-to)1325-1334
Number of pages10
JournalLaryngoscope
Volume112
Issue number8 I
StatePublished - 2002

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Spiral Ganglion
Dependovirus
Brain-Derived Neurotrophic Factor
Cell Survival
Cochlea
Neurons
Aminoglycosides
Auditory Hair Cells
Sodium Potassium Chloride Symporter Inhibitors
Cochlear Implantation
Nerve Degeneration
Nerve Growth Factors
Green Fluorescent Proteins
In Vitro Techniques
Reporter Genes
Electric Stimulation
Control Groups

Keywords

  • Brain-derived growth factor
  • Cochlea
  • Gene therapy
  • Ototoxicity
  • Spiral ganglion neurons

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

In vitro and in vivo assessment of the ability of adeno-associated virus - Brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult. / Lalwani, Anil K.; Han, Jay J.; Castelein, Caley M.; Carvalho, Gerard J.; Mhatre, Anand N.

In: Laryngoscope, Vol. 112, No. 8 I, 2002, p. 1325-1334.

Research output: Contribution to journalArticle

Lalwani, Anil K. ; Han, Jay J. ; Castelein, Caley M. ; Carvalho, Gerard J. ; Mhatre, Anand N. / In vitro and in vivo assessment of the ability of adeno-associated virus - Brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult. In: Laryngoscope. 2002 ; Vol. 112, No. 8 I. pp. 1325-1334.
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abstract = "Objectives/Hypothesis: Auditory dysfunction following ototoxic insult results from loss of cochlear hair cells. Secondary degeneration of auditory neurons ensues from withdrawal of neurotrophic support from hair cells and can be prevented with administration of neurotrophins. Administration of adeno-associated virus containing the gene for brain-derived neurotrophic factor will promote spiral ganglion neuron survival after the destruction of hair cells. Methods: Prevention of aminoglycoside-induced spiral ganglion neuron loss through the expression of brain-derived neurotrophic factor mediated by means of the adeno-associated virus was tested in vitro in cochlear explants and in vivo in mammalian cochlea. Results: Neuronal survival was significantly enhanced in adeno-associated virus-brain-derived neurotrophic factor transfected rat cochlear explants compared with control samples (30{\%} vs. 19{\%}, P <.05) following exposure to aminoglycoside. Following deafening with aminoglycoside and loop diuretic and introduction of adeno-associated virus-brain-derived neurotrophic factor through osmotic minipump, the experimental group of animals infused with adeno-associated virus-brain-derived neurotrophic factor displayed enhanced spiral ganglion neuron survival in the basal turn of the cochlea when compared with the control group infused with adeno-associated virus containing green fluorescent protein reporter gene. Conclusions: Administration of adeno-associated virus-brain-derived neurotrophic factor enhances spiral ganglion neuron survival following ototoxic exposure in vitro and in vivo. These studies lay the groundwork for further exploration of its application as an adjunct therapy for patients undergoing cochlear implantation because the success of implantation depends directly on the population of neurons available for electrical stimulation.",
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AU - Han, Jay J.

AU - Castelein, Caley M.

AU - Carvalho, Gerard J.

AU - Mhatre, Anand N.

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