Journal article
Anti-inflammatory Therapy Protects Spiral Ganglion Neurons After Aminoglycoside Antibiotic-Induced Hair Cell Loss
Neurotherapeutics, Vol.20(2), pp.578-601
03/2023
DOI: 10.1007/s13311-022-01336-2
PMCID: PMC10121993
PMID: 36697994
Abstract
Destruction of cochlear hair cells by aminoglycoside antibiotics leads to gradual death of the spiral ganglion neurons (SGNs) that relay auditory information to the brain, potentially limiting the efficacy of cochlear implants. Because the reasons for this cochlear neurodegeneration are unknown, there are no neuroprotective strategies for patients. To investigate this problem, we assessed transcriptomic changes in the rat spiral ganglion following aminoglycoside antibiotic (kanamycin)-induced hair cell destruction. We observed selectively increased expression of immune and inflammatory response genes and increased abundance of activated macrophages in spiral ganglia by postnatal day 32 in kanamycin-deafened rats, preceding significant SGN degeneration. Treatment with the anti-inflammatory medications dexamethasone and ibuprofen diminished long-term SGN degeneration. Ibuprofen and dexamethasone also diminished macrophage activation. Efficacy of ibuprofen treatment was augmented by co-administration of the nicotinamide adenine dinucleotide-stabilizing agent P7C3-A20. Our results support a critical role of neuroinflammation in SGN degeneration after aminoglycoside antibiotic-mediated cochlear hair cell loss, as well as a neuroprotective strategy that could improve cochlear implant efficacy.
Details
- Title: Subtitle
- Anti-inflammatory Therapy Protects Spiral Ganglion Neurons After Aminoglycoside Antibiotic-Induced Hair Cell Loss
- Creators
- Muhammad T Rahman - University of IowaErin M Bailey - Department of Biology, University of Iowa, Iowa City, IA, 52242, USABenjamin M Gansemer - Department of Biology, University of Iowa, Iowa City, IA, 52242, USAAndrew A Pieper - Case Western Reserve UniversityJ Robert Manak - Department of Pediatrics, University of Iowa, Iowa City, IA, 52242, USASteven H Green - Department of Biology, University of Iowa, Iowa City, IA, 52242, USA. steven-green@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Neurotherapeutics, Vol.20(2), pp.578-601
- DOI
- 10.1007/s13311-022-01336-2
- PMID
- 36697994
- PMCID
- PMC10121993
- NLM abbreviation
- Neurotherapeutics
- ISSN
- 1933-7213
- eISSN
- 1878-7479
- Grant note
- DC015790 / NIDCD NIH HHS DC002961 / NIDCD NIH HHS DE021071 / NIDCR NIH HHS
- Language
- English
- Electronic publication date
- 01/25/2023
- Date published
- 03/2023
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center; Otolaryngology
- Record Identifier
- 9984363420702771
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