Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1264 2023-05-31 15:16:37 |
2 format correct Meta information modification 1264 2023-06-05 04:12:33 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Smith-Cortinez, N.; Tan, A.K.; Stokroos, R.J.; Versnel, H.; Straatman, L.V. Hearing Loss and Its Pathophysiology. Encyclopedia. Available online: https://encyclopedia.pub/entry/45066 (accessed on 13 June 2024).
Smith-Cortinez N, Tan AK, Stokroos RJ, Versnel H, Straatman LV. Hearing Loss and Its Pathophysiology. Encyclopedia. Available at: https://encyclopedia.pub/entry/45066. Accessed June 13, 2024.
Smith-Cortinez, Natalia, A. Katherine Tan, Robert J. Stokroos, Huib Versnel, Louise V. Straatman. "Hearing Loss and Its Pathophysiology" Encyclopedia, https://encyclopedia.pub/entry/45066 (accessed June 13, 2024).
Smith-Cortinez, N., Tan, A.K., Stokroos, R.J., Versnel, H., & Straatman, L.V. (2023, May 31). Hearing Loss and Its Pathophysiology. In Encyclopedia. https://encyclopedia.pub/entry/45066
Smith-Cortinez, Natalia, et al. "Hearing Loss and Its Pathophysiology." Encyclopedia. Web. 31 May, 2023.
Hearing Loss and Its Pathophysiology
Edit

Sensorineural hearing loss is caused by damage to sensory hair cells and/or spiral ganglion neurons. In non-mammalian species, hair cell regeneration after damage is observed, even in adulthood. Although the neonatal mammalian cochlea carries regenerative potential, the adult cochlea cannot regenerate lost hair cells. The survival of supporting cells with regenerative potential after cochlear trauma in adults is promising for promoting hair cell regeneration through therapeutic approaches. 

inner ear regeneration endogenous progenitor cells re-innervation

1. Introduction

Hearing loss is the most frequent sensory deficit in humans and is mainly caused by irreversible damage to cochlear sensory cells (hair cells) and/or their associated neurons (spiral ganglion neurons, SGNs). Irreversible hair cell loss is particularly caused by aging, noise exposure and ototoxic medication. In 2019, there were approximately 460 million individuals with disabling hearing loss, and according to the WHO, this number might increase to more than 900 million individuals by 2050 [1]. Hearing loss, which is often accompanied by tinnitus, results in high levels of morbidity, depression and social isolation, and it has been shown to significantly contribute to cognitive decline in the elderly [2][3][4][5][6][7][8]. While hearing aids and cochlear implants restore hearing in hearing-impaired and deaf individuals to a large extent, sounds are still perceived as distorted (for the sound of a cochlear implant, see [9] because the original cochlear function—in which the hair cells together with the basilar membrane play a key role—is not replaced.
To prevent hair cell loss, there are currently several otoprotectants that can potentially prevent damage after ototoxic or noise-induced trauma, including antioxidants to reduce oxidative stress (such as sodium thiosulfate, amifostine, N-acetylcysteine) or anti-inflammatory medication, such as dexamethasone (for review on ototoxicity see [10] and for review on noise-induced hearing loss (NIHL) see [11]). Regeneration of lost cochlear cells has potential as an alternative approach and can have significant clinical applications to restore hearing without the need for an electronic device. Studies on the regeneration of the avian cochlea or zebrafish lateral line have demonstrated spontaneous hair cell regeneration out of endogenous progenitor cells after damage, even in adult specimens [12][13]. In contrast, the mammalian adult inner ear possesses limited regenerative potential [14][15]. The vestibular organ shows scarce but spontaneous hair cell regeneration after damage, whereas the cochlea shows no spontaneous regeneration [16]. For non-genetic hearing loss, targeting the endogenous cochlear progenitor cells by manipulating signaling pathways to promote hair cell renewal might improve the regenerative capacity.
Previous studies on the mammalian cochlea have mainly evaluated the presence of endogenous progenitor cells in the neonatal cochlea or in a normal hearing condition [17][18][19][20][21][22][23]. The effects of trauma, such as ototoxicity or noise exposure, on regenerative capacity of the cochlea of adult mammals has been scarcely studied. Because the majority of patients with SNHL are adults, studying the regenerative capacity after hair cell ablation in the adult mammalian cochlea is the key to understanding its true therapeutic potential. Importantly, the pathways that regulate cochlear development in mammals and hair cell regeneration in non-mammalian vertebrates shed light on the steps needed to improve mammalian hair cell regeneration in the future.

2. Hearing Loss and Its Pathophysiology

2.1. Age-Related Hearing Loss

Age-related hearing loss (presbyacusis) is the most common sensory impairment in the elderly, and with aging of the population, the number of affected people is expected to rise rapidly [24]. Several age-related structural changes have been described, including age-related hair cell loss, SGN loss and atrophy of the stria vascularis [25]. Over the last decade, studies have also shown loss of inner hair cell (IHC) synapses and their afferent fibers [26][27].
Based on histopathology and patterns of hearing loss, Schuknecht et al. classified four main types of presbyacusis, including (1) sensory (hair cell loss at basal end of cochlea), (2) strial or metabolic (correlated to atrophy in the stria vascularis), (3) neural (as a result of loss of cochlear neurons), and (4) cochlear conductive or mechanical presbyacusis (due to stiffness of the basilar membrane) [27][28]. They concluded that the main contributing factor to presbyacusis was atrophy of the stria vascularis. Interestingly, more recently, it has been shown that presbyacusis is predominantly associated with damage to sensory cells, rather than age-related changes in stria vascularis [29].
The precise mechanism underlying age-related degeneration of different cochlear structures is unknown. Several contributing factors have been described, including inflammatory changes [30], genetic factors [31] and oxidative stress [32]. Although age-related changes are multifactorial, noise exposure is thought to be the major contributing factor of presbyacusis [29][33].

2.2. Noise-Induced Hearing Loss

NIHL mainly causes damage to and loss of outer hair cells (OHCs). Depending on the duration and intensity of the noise exposure, there may be IHC loss as well. Three mechanisms of noise-induced cochlear damage can be distinguished: (1) mechanical destruction by short exposure to extreme noise intensities causing direct trauma; (2) metabolic decompensation after noise exposure, which occurs over a longer period of time in high intensities; and/or (3) IHC synaptopathy leading to loss of SGNs [11][34][35]. Excessive noise stimulation causes the formation of free radicals or reactive oxygen species (ROS), as well as glutamate excitotoxicity, followed by activation of signaling pathways leading to cell death [36]. For an extensive review on cellular mechanisms involved in NIHL, see [34].
Apart from the loss of sensory cells, it has been widely investigated that noise exposure causes permanent damage to the ribbon synapses of the IHCs, also referred to as cochlear synaptopathy [35][37][38]. This leads to supra-threshold hearing loss, i.e., no measurable increase in hearing threshold but worse hearing at supra-threshold levels (including reduced speech perception in noise, hyperacusis) and tinnitus, also known as hidden hearing loss [35][38][39][40].

2.3. Ototoxicity

Ototoxicity is a pharmacological adverse reaction that causes irreversible damage to the hair cells in cochlear and vestibular tissue, leading to their functional loss. With over a million cases of profound ototoxicity-induced hearing loss annually worldwide, this is a major problem [41]. There are more than 600 categories of drugs registered with ototoxic side effects, and this number is still increasing [42]. The two most important ototoxic drugs are aminoglycosides (including gentamicin and kanamycin) and platinum-based antineoplastic agents (such as cisplatin, oxaliplatin and carboplatin). Numerous studies have been performed evaluating the effects of ototoxicity on the cochlea (for review, see [43]). Ototoxicity causes mainly OHC loss in a basal to apical gradient, thus associated with especially high frequency hearing loss. With higher concentrations or persistent exposure, ototoxic damage progresses to IHC loss as well. The mechanism by which ototoxic drugs affect the cochlea has not yet been fully elucidated. It has been suggested that oxidative stress induces apoptosis and necrosis in hair cells and marginal cells in the stria vascularis (for a review, see [44]). Ototoxins enter cells via active transport [45][46][47][48]. It has been recently shown that inflammation precedes oxidative stress and excessive production of ROS; therefore, it has been suggested that the inflammatory response triggers cell death [49]. After apoptosis of hair cells, the cell is extruded from the sensory epithelium and supporting cells phagocytize the remaining cell fragments. Supporting cells form a scar and preserve the epithelial cytoarchitecture and the integrity of the barrier of the organ of Corti [50][51][52]. Hair cell loss may occur rapidly (within days) after ototoxic exposure; following IHC loss, SGNs first become smaller and subsequently progressive SGN loss occurs [53]. The loss of SGNs has been associated with discontinued neurotrophic support from the organ of Corti [54][55].
Hair cell loss may occur rapidly (within days) after ototoxic exposure; following IHC loss, SGNs first become smaller and subsequently progressive SGN loss occurs [53]. Previous studies on ototoxicity have mainly focused on ototoxicity-induced hair cell loss and considered neuronal loss to be a secondary consequence caused by loss of trophic support [56][57][58][59][60][61]. However, as in NIHL, direct ototoxicity-induced damage to the synapse and SGNs may occur, as well as ototoxicity-induced swelling of the nerve [62][63][64][65].

References

  1. Wilson, B.S.; Tucci, D.L.; Merson, M.H.; O’Donoghue, G.M. Global hearing health care: New findings and perspectives. Lancet 2017, 390, 2503–2515.
  2. Cosh, S.; Helmer, C.; Delcourt, C.; Robins, T.G.; Tully, P.J. Depression in elderly patients with hearing loss: Current perspectives. Clin. Interv. Aging 2019, 14, 1471–1480.
  3. Kramer, S.E.; Kapteyn, T.S.; Kuik, D.J.; Deeg, D.J.H. The Association of Hearing Impairment and Chronic Diseases with Psychosocial Health Status in Older Age. J. Aging Health 2002, 14, 122–137.
  4. Li, C.-M.; Zhang, X.; Hoffman, H.J.; Cotch, M.F.; Themann, C.L.; Wilson, M.R. Hearing Impairment Associated with Depression in US Adults, National Health and Nutrition Examination Survey 2005–2010. JAMA Otolaryngol. Neck Surg. 2014, 140, 293–302.
  5. Lin, F.R.; Yaffe, K.; Xia, J.; Xue, Q.-L.; Harris, T.B.; Purchase-Helzner, E.; Satterfield, S.; Ayonayon, H.N.; Ferrucci, L.; Simonsick, E.M.; et al. Hearing Loss and Cognitive Decline in Older Adults. JAMA Intern. Med. 2013, 173, 293–299.
  6. Loughrey, D.G.; Kelly, M.E.; Kelley, G.A.; Brennan, S.; Lawlor, B.A. Association of age-related hearing loss with cognitive function, cognitive impairment, and dementia: A systematic review and meta-analysis. JAMA Otolaryngol.–Head Neck Surg. 2018, 144, 115–126.
  7. Monzani, D.; Galeazzi, G.M.; Genovese, E.; Marrara, A.; Martini, A. Psychological profile and social behaviour of working adults with mild or moderate hearing loss. Acta Otorhinolaryngol. Ital. 2008, 28, 61–66.
  8. Powell, D.S.; Oh, E.S.; Lin, F.R.; Deal, J.A. Hearing Impairment and Cognition in an Aging World. J. Assoc. Res. Otolaryngol. 2021, 22, 387–403.
  9. Peters, J.P.M.; Wendrich, A.W.; van Eijl, R.H.M.; Rhebergen, K.S.; Versnel, H.; Grolman, W. The Sound of a Cochlear Implant Investigated in Patients with Single-Sided Deafness and a Cochlear Implant. Otol. Neurotol. 2018, 39, 707–714.
  10. Waissbluth, S. Clinical trials evaluating transtympanic otoprotectants for cisplatin-induced ototoxicity: What do we know so far? Eur. Arch. Oto-Rhino-Laryngol. 2020, 277, 2413–2422.
  11. Le, T.N.; Straatman, L.V.; Lea, J.; Westerberg, B. Current insights in noise-induced hearing loss: A literature review of the underlying mechanism, pathophysiology, asymmetry, and management options. J. Otolaryngol.—Head Neck Surg. 2017, 46, 41.
  12. Brignull, H.R.; Raible, D.W.; Stone, J.S. Feathers and fins: Non-mammalian models for hair cell regeneration. Brain Res. 2009, 1277, 12–23.
  13. Bermingham-McDonogh, O.; Rubel, E.W. Hair cell regeneration: Winging our way towards a sound future. Curr. Opin. Neurobiol. 2003, 13, 119–126.
  14. Taylor, R.R.; Jagger, D.J.; Forge, A. Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea. PLoS ONE 2012, 7, e30577.
  15. Matsui, J.I.; Cotanche, D.A. Sensory hair cell death and regeneration: Two halves of the same equation. Curr. Opin. Otolaryngol. Head Neck Surg. 2004, 12, 418–425.
  16. Burns, J.C.; Stone, J.S. Development and regeneration of vestibular hair cells in mammals. Semin. Cell Dev. Biol. 2017, 65, 96–105.
  17. Bramhall, N.F.; Shi, F.; Arnold, K.; Hochedlinger, K.; Edge, A.S. Lgr5-Positive Supporting Cells Generate New Hair Cells in the Postnatal Cochlea. Stem Cell Rep. 2014, 2, 311–322.
  18. Cox, B.C.; Chai, R.; Lenoir, A.; Liu, Z.; Zhang, L.; Nguyen, D.-H.; Chalasani, K.; Steigelman, K.A.; Fang, J.; Rubel, E.W.; et al. Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development 2014, 141, 816–829.
  19. Chai, R.; Kuo, B.; Wang, T.; Liaw, E.J.; Xia, A.; Jan, T.A.; Liu, Z.; Taketo, M.M.; Oghalai, J.S.; Nusse, R.; et al. Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Proc. Natl. Acad. Sci. USA 2012, 109, 8167–8172.
  20. Zhang, Y.; Chen, Y.; Ni, W.; Guo, L.; Lu, X.; Liu, L.; Li, W.; Sun, S.; Wang, L.; Li, H. Dynamic expression of Lgr6 in the developing and mature mouse cochlea. Front. Cell. Neurosci. 2015, 9, 165.
  21. Oesterle, E.C.; Campbell, S.; Taylor, R.R.; Forge, A.; Hume, C.R. Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear. J. Assoc. Res. Otolaryngol. 2008, 9, 65–89.
  22. Shi, F.; Kempfle, J.S.; Edge, A.S.B. Wnt-Responsive Lgr5-Expressing Stem Cells Are Hair Cell Progenitors in the Cochlea. J. Neurosci. 2012, 32, 9639–9648.
  23. Żak, M.; van Oort, T.; Hendriksen, F.G.; Garcia, M.-I.; Vassart, G.; Grolman, W. LGR4 and LGR5 Regulate Hair Cell Differentiation in the Sensory Epithelium of the Developing Mouse Cochlea. Front. Cell. Neurosci. 2016, 10, 186.
  24. WHO. Addressing the Rising Prevalence of Hearing Loss; World Health Organization: Geneva, Switzerland, 2018.
  25. Merchant, S.N.; Tsuji, K.; Wall, I.C.; Velázquez-Villaseñor, L.; Glynn, R.J.; Rauch, S.D. Temporal Bone Studies of the Human Peripheral Vestibular System. Normative Vestibular Hair Cell Data. Ann. Otol. Rhinol. Laryngol. 2000, 109, 3–13.
  26. Viana, L.M.; O’Malley, J.T.; Burgess, B.J.; Jones, D.D.; Oliveira, C.A.; Santos, F.; Merchant, S.N.; Liberman, L.D.; Liberman, M.C. Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue. Hear. Res. 2015, 327, 78–88.
  27. Schuknecht, H.F.; Gacek, M.R. Cochlear Pathology in Presbycusis. Ann. Otol. Rhinol. Laryngol. 1993, 102, 1–16.
  28. Schuknecht, H.F. Further Observations on the Pathology of Presbycusis. Arch. Otolaryngol. Neck Surg. 1964, 80, 369–382.
  29. Wu, P.-Z.; O’Malley, J.T.; De Gruttola, V.; Liberman, M.C. Age-Related Hearing Loss Is Dominated by Damage to Inner Ear Sensory Cells, Not the Cellular Battery That Powers Them. J. Neurosci. 2020, 40, 6357–6366.
  30. Fujioka, M.; Okano, H.; Ogawa, K. Inflammatory and immune responses in the cochlea: Potential therapeutic targets for sensorineural hearing loss. Front. Pharmacol. 2014, 5, 287.
  31. Tawfik, K.O.; Klepper, K.; Saliba, J.; Friedman, R.A. Advances in understanding of presbycusis. J. Neurosci. Res. 2020, 98, 1685–1697.
  32. Paplou, V.; Schubert, N.M.A.; Pyott, S.J. Age-Related Changes in the Cochlea and Vestibule: Shared Patterns and Processes. Front. Neurosci. 2021, 15, 680856.
  33. Keithley, E.M. Pathology and mechanisms of cochlear aging. J. Neurosci. Res. 2020, 98, 1674–1684.
  34. Kurabi, A.; Keithley, E.M.; Housley, G.D.; Ryan, A.F.; Wong, A.C.-Y. Cellular mechanisms of noise-induced hearing loss. Hear. Res. 2017, 349, 129–137.
  35. Kujawa, S.G.; Liberman, M.C. Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss. J. Neurosci. 2009, 29, 14077–14085.
  36. Yamane, H.; Nakai, Y.; Takayama, M.; Iguchi, H.; Nakagawa, T.; Kojima, A. Appearance of free radicals in the guinea pig inner ear after noise-induced acoustic trauma. Eur. Arch. Oto-Rhino-Laryngol. 1995, 252, 504–508.
  37. Robertson, D. Functional significance of dendritic swelling after loud sounds in the guinea pig cochlea. Hear. Res. 1983, 9, 263–278.
  38. Shi, L.; Chang, Y.; Li, X.; Aiken, S.; Liu, L.; Wang, J. Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss. Neural Plast. 2016, 2016, 6143164.
  39. Moser, T.; Predoehl, F.; Starr, A. Review of Hair Cell Synapse Defects in Sensorineural Hearing Impairment. Otol. Neurotol. 2013, 34, 995–1004.
  40. Cunningham, L.L.; Tucci, D.L. Restoring Synaptic Connections in the Inner Ear after Noise Damage. N. Engl. J. Med. 2015, 372, 181–182.
  41. O’Sullivan, M.; Perez, A.; Lin, R.; Sajjadi, A.; Ricci, A.J.; Cheng, A.G. Towards the Prevention of Aminoglycoside-Related Hearing Loss. Front. Cell. Neurosci. 2017, 11, 325.
  42. Cianfrone, G.; Pentangelo, D.; Cianfrone, F.; Mazzei, F.; Turchetta, R.; Orlando, M.P.; Altissimi, G. Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: A reasoned and updated guide. Eur. Rev. Med. Pharmacol. Sci. 2011, 15, 601–636.
  43. Lanvers-Kaminsky, C.; Zehnhoff-Dinnesen, A.A.; Parfitt, R.; Ciarimboli, G. Drug-induced ototoxicity: Mechanisms, Pharmacogenetics, and protective strategies. Clin. Pharmacol. Ther. 2017, 101, 491–500.
  44. González-González, S. The role of mitochondrial oxidative stress in hearing loss. Neurol. Disord. Ther. 2017, 1, 1–5.
  45. Alharazneh, A.; Luk, L.; Huth, M.; Monfared, A.; Steyger, P.S.; Cheng, A.G.; Ricci, A.J. Functional Hair Cell Mechanotransducer Channels Are Required for Aminoglycoside Ototoxicity. PLoS ONE 2011, 6, e22347.
  46. Nagai, J.; Takano, M. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways. Biochem. Pharmacol. 2014, 90, 331–337.
  47. Steyger, P.S. Cellular Uptake of Aminoglycosides. Volta Rev. 2005, 105, 299–324.
  48. Sheth, S.; Mukherjea, D.; Rybak, L.P.; Ramkumar, V. Mechanisms of Cisplatin-Induced Ototoxicity and Otoprotection. Front. Cell Neurosci. 2017, 11, 338.
  49. Gentilin, E.; Simoni, E.; Candito, M.; Cazzador, D.; Astolfi, L. Cisplatin-Induced Ototoxicity: Updates on Molecular Targets. Trends Mol. Med. 2019, 25, 1123–1132.
  50. Raphael, Y.; Altschuler, R.A. Scar formation after drug-induced cochlear insult. Hear. Res. 1991, 51, 173–183.
  51. Forge, A. Outer hair cell loss and supporting cell expansion following chronic gentamicin treatment. Hear. Res. 1985, 19, 171–182.
  52. Anttonen, T.; Belevich, I.; Kirjavainen, A.; Laos, M.; Brakebusch, C.; Jokitalo, E.; Pirvola, U. How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse. J. Assoc. Res. Otolaryngol. 2014, 15, 975–992.
  53. van Loon, M.C.; Ramekers, D.; Agterberg, M.J.; de Groot, J.C.; Grolman, W.; Klis, S.F.; Versnel, H. Spiral ganglion cell morphology in guinea pigs after deafening and neurotrophic treatment. Hear. Res. 2013, 298, 17–26.
  54. Ramekers, D.; Versnel, H.; Grolman, W.; Klis, S.F. Neurotrophins and their role in the cochlea. Hear. Res. 2012, 288, 19–33.
  55. Zilberstein, Y.; Liberman, M.C.; Corfas, G. Inner Hair Cells Are Not Required for Survival of Spiral Ganglion Neurons in the Adult Cochlea. J. Neurosci. 2012, 32, 405–410.
  56. Bae, W.Y.; Kim, L.S.; Hur, D.Y.; Jeong, S.W.; Kim, J.R. Secondary Apoptosis of Spiral Ganglion Cells Induced by Aminoglycoside: Fas–Fas Ligand Signaling Pathway. Laryngoscope 2008, 118, 1659–1668.
  57. Dodson, H.; Mohuiddin, A. Response of spiral ganglion neurones to cochlear hair cell destruction in the guinea pig. J. Neurocytol. 2000, 29, 525–537.
  58. McFadden, S.L.; Ding, D.; Jiang, H.; Salvi, R.J. Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla. Brain Res. 2004, 997, 40–51.
  59. Takeno, S.; Wake, M.; Mount, R.J.; Harrison, R.V. Degeneration of Spiral Ganglion Cells in the Chinchilla afterInner H air Cell Loss Induced by Carboplatin. Audiol. Neurotol. 1998, 3, 281–290.
  60. Havenith, S.; Klis, S.F.L.; Versnel, H.; Grolman, W. A Guinea Pig Model of Selective Severe High-Frequency Hearing Loss. Otol. Neurotol. 2013, 34, 1510–1518.
  61. Versnel, H.; Agterberg, M.J.; de Groot, J.C.; Smoorenburg, G.F.; Klis, S.F. Time course of cochlear electrophysiology and morphology after combined administration of kanamycin and furosemide. Hear. Res. 2007, 231, 1–12.
  62. Basile, A.S.; Huang, J.-M.; Xie, C.; Webster, D.; Berlin, C.; Skolnick, P. N-Methyl-D-aspartate antagonists limit aminoglycoside antibiotic–induced hearing loss. Nat. Med. 1996, 2, 1338–1343.
  63. Duan, M.; Agerman, K.; Ernfors, P.; Canlon, B. Complementary roles of neurotrophin 3 and a N-Methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity. Proc. Natl. Acad. Sci. USA 2000, 97, 7597–7602.
  64. Ruan, Q.; Ao, H.; He, J.; Chen, Z.; Yu, Z.; Zhang, R.; Wang, J.; Yin, S. Topographic and quantitative evaluation of gentamicin-induced damage to peripheral innervation of mouse cochleae. Neurotoxicology 2014, 40, 86–96.
  65. Sargsyan, L.; Hetrick, A.P.; Gonzalez, J.G.; Leek, M.R.; Martin, G.K.; Li, H. Effects of combined gentamicin and furosemide treatment on cochlear ribbon synapses. Neurotoxicology 2021, 84, 73–83.
More
Information
Subjects: Others
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , , ,
View Times: 221
Revisions: 2 times (View History)
Update Date: 05 Jun 2023
1000/1000
Video Production Service