TY - JOUR
T1 - Is cochlear synapse loss an origin of low-frequency hearing loss associated with endolymphatic hydrops?
AU - Valenzuela, Carla V.
AU - Lee, Choongheon
AU - Mispagel, Abby
AU - Bhattacharyya, Atri
AU - Lefler, Shannon M.
AU - Payne, Shelby
AU - Goodman, Shawn S.
AU - Ortmann, Amanda J.
AU - Buchman, Craig A.
AU - Rutherford, Mark A.
AU - Lichtenhan, Jeffery T.
N1 - Funding Information:
We thank Dr. Dorina Kallogjeri for assistance with the statistical analysis, and Dr. John J. Guinan, Jr. for critiquing an earlier version of this manuscript. We thank two reviewers for their helpful comments. This research was supported by the American Academy of Otolaryngology- Head and Neck Surgery Foundation Centralized Otolaryngology Research Efforts, through the AAO-HNSF Resident Research Award (C.V.V.), the National Institute of Deafness and Other Communication Disorders within the National Institutes of Health, through R01 DC014997 (J.T.L.), R01 DC014712 (M.A.R.), and the “Development of Clinician/Researchers in Academic ENT” training grant T32 DC000022 (C.V.V.).
Publisher Copyright:
© 2020
PY - 2020/12
Y1 - 2020/12
N2 - There is a strong association between endolymphatic hydrops and low-frequency hearing loss, but the origin of the hearing loss remains unknown. A reduction in the number of cochlear afferent synapses between inner hair cells and auditory nerve fibres may be the origin of the low-frequency hearing loss, but this hypothesis has not been directly tested in humans or animals. In humans, measurements of hearing loss and postmortem temporal-bone based measurements of endolymphatic hydrops are generally separated by large amounts of time. In animals, there has not been a good objective, physiologic, and minimally invasive measurement of low-frequency hearing. We overcame this obstacle with the combined use of a reliable surgical approach to ablate the endolymphatic sac in guinea pigs and create endolymphatic hydrops, the Auditory Nerve Overlapped Waveform to measure low-frequency hearing loss (≤ 1 kHz), and immunohistofluorescence-based confocal microscopy to count cochlear synapses. Results showed low- and mid-(1–4 kHz) frequency hearing loss at all postoperative days, 1, 4, and 30. There was no statistically significant loss of cochlear synapses, and there was no correlation between synapse loss and hearing function. We conclude that cochlear afferent synaptic loss is not the origin of the low-frequency hearing loss in the early days following endolymphatic sac ablation. Understanding what is, and is not, the origin of a hearing loss can help guide preventative and therapeutic development.
AB - There is a strong association between endolymphatic hydrops and low-frequency hearing loss, but the origin of the hearing loss remains unknown. A reduction in the number of cochlear afferent synapses between inner hair cells and auditory nerve fibres may be the origin of the low-frequency hearing loss, but this hypothesis has not been directly tested in humans or animals. In humans, measurements of hearing loss and postmortem temporal-bone based measurements of endolymphatic hydrops are generally separated by large amounts of time. In animals, there has not been a good objective, physiologic, and minimally invasive measurement of low-frequency hearing. We overcame this obstacle with the combined use of a reliable surgical approach to ablate the endolymphatic sac in guinea pigs and create endolymphatic hydrops, the Auditory Nerve Overlapped Waveform to measure low-frequency hearing loss (≤ 1 kHz), and immunohistofluorescence-based confocal microscopy to count cochlear synapses. Results showed low- and mid-(1–4 kHz) frequency hearing loss at all postoperative days, 1, 4, and 30. There was no statistically significant loss of cochlear synapses, and there was no correlation between synapse loss and hearing function. We conclude that cochlear afferent synaptic loss is not the origin of the low-frequency hearing loss in the early days following endolymphatic sac ablation. Understanding what is, and is not, the origin of a hearing loss can help guide preventative and therapeutic development.
KW - Auditory Nerve Overlapped Waveform
KW - Endolymphatic hydrops
KW - Low-frequency hearing loss
KW - Ménière's disease
KW - Ribbon synapse
UR - http://www.scopus.com/inward/record.url?scp=85094152654&partnerID=8YFLogxK
U2 - 10.1016/j.heares.2020.108099
DO - 10.1016/j.heares.2020.108099
M3 - Article
C2 - 33125982
AN - SCOPUS:85094152654
SN - 0378-5955
VL - 398
JO - Hearing research
JF - Hearing research
M1 - 108099
ER -