Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons

Details

• Personal Author:
  Ding D ; Gao K ; Roth J ; Salvi R ; Sun H
• Description:
  Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life-threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants. In both adult and postnatal day 3 cultures, hair cell damage began at the base of the cochleae and progressed toward the apex in a dose-dependent manner. In postnatal day 3 cultures, spiral ganglion neurons were rapidly destroyed by kanamycin prior to hair cell loss. In contrast, adult spiral ganglion neurons were resistant to kanamycin damage even at the highest concentration, consistent with in vivo models of delayed SGN degeneration. In postnatal day 3 cultures, kanamycin preferentially damaged type I spiral ganglion neurons, whereas type II neurons were resistant. Spiral ganglion degeneration of postnatal day 3 neurons was associated with upregulation of the superoxide radical and caspase-3-mediated cell death. These results show for the first time that kanamycin is toxic to postnatal day 3 spiral ganglion neurons, but not adult neurons. [Description provided by NIOSH]
• Subjects:
  Animals Anti-Bacterial Agents Laboratories Occupational Health Particulate Matter Pathology Safety
• Keywords:
  Antibiotics Auditory Nerve Author Keywords: Auditory Nerve Fibers Bacterial Infections Caspase-3 Cell Damage Fibers Hair Cells In Vivo Study Kanamycin Laboratory Animals Models Ototoxicity Spiral Ganglion Neurons

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• ISSN:
  1029-8428
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  32
• Issue:
  4
• NIOSHTIC Number:
  nn:20051166
• Citation:
  Neurotox Res 2017 Nov; 32(4):603-613
• Contact Point Address:
  Richard Salvi, Department of Otolaryngology Head and Neck Surgery, Xiang Ya Hospital, Central South University, Changsha, Hunan 410013, China
• Email:
  salvi@buffalo.edu
• Federal Fiscal Year:
  2018
• Performing Organization:
  State University of New York - Buffalo
• Peer Reviewed:
  True
• Start Date:
  20120901
• Source Full Name:
  Neurotoxicity Research
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6b6efbba42018fe03f9e44e0c5de118103cec2ba27f41e23efd9d218113d9e3abb2d7f8958fed47ec2ccfb890bbdf7b89fc64bec26f215b5d0381bd1488c36c3
• Download URL:
  https://stacks.cdc.gov/view/cdc/211260/cdc_211260_DS1.pdf
• File Type:
  [PDF - 17.80 MB ]