{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:59:55Z","timestamp":1785268795412,"version":"3.55.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Aminoglycosides (AG) antibiotics are a common treatment for recurrent infections in cystic fibrosis (CF) patients. AGs are highly ototoxic, resulting in a range of auditory dysfunctions. It was recently shown that the acoustic startle reflex (ASR) can assess behavioral evidence of hyperacusis and tinnitus in an amikacin cochleotoxicity mouse model. The goal of this study was to establish if tobramycin treatment led to similar changes in ASR behavior and to establish whether ebselen can prevent the development of these maladaptive neuroplastic symptoms. CBA\/Ca mice were divided into three groups: Group 1 served as a control and did not receive tobramycin or ebselen, Group 2 received tobramycin (200 mg\/kg\/s.c.) and the vehicle (DMSO\/saline\/i.p.) daily for 14 continuous days, and Group 3 received the same dose\/schedule of tobramycin as Group 2 and ebselen at (20 mg\/kg\/i.p.). Auditory brainstem response (ABR) and ASR hearing assessments were collected at baseline and 2, 6, 10, 14, and 18 weeks from the start of treatment. ASR tests included input\/output (I\/O) functions which assess general hearing and hyperacusis, and Gap-induced prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus. At 18 weeks, histologic analysis showed predominantly normal appearing hair cells and spiral ganglion neuron (SGN) synapses. Following 14 days of tobramycin injections, 16 kHz thresholds increased from baseline and fluctuated over the 18-week recovery period. I\/O functions revealed exaggerated startle response magnitudes in 50% of mice over the same period. Gap detection deficits, representing behavioral evidence of tinnitus, were observed in a smaller subset (36%) of animals. Interestingly, increases in ABR wave III\/wave I amplitude ratios were observed. These tobramycin data corroborate previous findings that AGs can result in hearing dysfunctions. We show that a 14-day course of tobramycin treatment can cause similar levels of hearing loss and tinnitus, when compared to a 14-day course of amikacin, but less hyperacusis. Evidence suggests that tinnitus and hyperacusis might be common side effects of AG antibiotics.<\/jats:p>","DOI":"10.3389\/fnmol.2021.715952","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:14:15Z","timestamp":1630714455000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity"],"prefix":"10.3389","volume":"14","author":[{"given":"Ryan J.","family":"Longenecker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rende","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Homan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Kil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118824","article-title":"Curcumin mitigates neurotoxic and neurobehavioral changes of gentamicin and sodium salicylate in rats by adjusting oxidative stress and apoptosis.","volume":"265","author":"Abd-Elhakim","year":"2021","journal-title":"Life Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1044\/policy.GL1994-00003","article-title":"Guidelines for the audiologic management of individuals receiving cochleotoxic drug therapy.","year":"1994","journal-title":"ASHA"},{"key":"B3","doi-asserted-by":"publisher","first-page":"30155","DOI":"10.1016\/j.bjorl.2020.09.002","article-title":"Protective effect of creatine on amikacin-induced ototoxicity.","author":"Apaydin","year":"2021","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00206","article-title":"Central gain control in tinnitus and hyperacusis.","volume":"5","author":"Auerbach","year":"2014","journal-title":"Front. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"290","DOI":"10.5152\/iao.2016.2617","article-title":"A prospective experimental study on the protective effect on resveratrol against amikacin-induced ototoxicity in rats.","volume":"12","author":"Avci","year":"2016","journal-title":"J. Int. Adv. Otol."},{"key":"B6","author":"Baguley","year":"2007","journal-title":"Hyperacusis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1007\/s00106-017-0464-3","article-title":"Hyperacusis: major research questions.","author":"Baguley","year":"2018"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2564","DOI":"10.1002\/jnr.221699","article-title":"Tinnitus and inferior colliculus activity in chinchillas related to three distinct patterns of cochlea trauma.","volume":"86","author":"Bauer","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00203","article-title":"Changes in the response properties of inferior colliculus neurons relating to tinnitus.","volume":"5","author":"Berger","year":"2014","journal-title":"Front. Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.neuroscience.2019.02.031","article-title":"Non-invasive assays of cochlear synaptopathy \u2013candidates and considerations.","volume":"407","author":"Bharadwaj","year":"2019","journal-title":"Neuroscience"},{"key":"B11","doi-asserted-by":"publisher","first-page":"12545","DOI":"10.1523\/JNEUROSCI.3042-10.2010","article-title":"Supporting cells eliminate dying sensory hair cells to maintain epithelial integrity in the avian inner ear.","volume":"30","author":"Bird","year":"2010","journal-title":"J. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1037\/\/0735-7044.111.6.1353","article-title":"Inbred mouse strains differ in the regulation of startle and prepulse inhibition of the startle response.","volume":"111","author":"Bullock","year":"1997","journal-title":"Behav. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9082412","article-title":"Association between hyperacusis and tinnitus.","volume":"9","author":"Cederroth","year":"2020","journal-title":"J. Clin. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1111\/ejn.12580","article-title":"Neural changes accompanying tinnitus following unilateral acoustic trauma in the guinea pig.","volume":"40","author":"Coomber","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"B15","first-page":"53","article-title":"Ototoxicity screening of patients treated with streptomycin using distortion product otoacoustic emissions.","volume":"10","author":"Daud","year":"2014","journal-title":"B-ENT"},{"key":"B16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/978-1-4899-2286-1_10","article-title":"The mammalian startle response","author":"Davis","year":"1984","journal-title":"Neural Mechanisms of Startle Behavior"},{"key":"B17","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/s0378-5955(01)00250-7","article-title":"Genetic basis for susceptibility to noise-induced hearing loss in mice.","volume":"155","author":"Davis","year":"2001","journal-title":"Hear. Res."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00124","article-title":"Thalamocortical dysrhythmia: a theoretical update in tinnitus.","volume":"6","author":"De Ridder","year":"2015","journal-title":"Front. Neurol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.573047","article-title":"Diffusible tumor necrosis factor-alpha (TNF-\u03b1) promotes noise-induced parvalbumin-positive (PV+) neuron loss and auditory processing impairments.","volume":"14","author":"Deng","year":"2020","journal-title":"Front. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.ijporl.2017.03.023","article-title":"Protective role of misoprostol in prevention of gentamicin ototoxicity.","volume":"96","author":"Dogan","year":"2017","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"7597","DOI":"10.1073\/pnas.97.13.7597","article-title":"Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity.","volume":"97","author":"Duan","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B22","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/bs.pbr.2020.01.006","article-title":"Separate auditory pathways for the induction and maintenance of tinnitus and hyperacusis.","volume":"260","author":"Eggermont","year":"2021","journal-title":"Prog. Brain Res."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00029","article-title":"Maladaptive neural synchrony in tinnitus: origin and restoration.","volume":"6","author":"Eggermont","year":"2015","journal-title":"Front. Neurol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"E8","DOI":"10.1177\/014556131809700802","article-title":"Protective effect of pentoxifylline on amikacin-induced ototoxicity.","volume":"97","author":"El-Anwar","year":"2018","journal-title":"Ear Nose Throat J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.jcf.2020.08.002","article-title":"The implementation of an aminoglycoside induced ototoxicity algorithm for people with cystic fibrosis.","volume":"20","author":"Elson","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"B26","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nature09656","article-title":"Reversing pathological neural activity using targeted plasticity.","volume":"470","author":"Engineer","year":"2011","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nm0496-463","article-title":"Protection of auditory neurons from aminoglycoside toxicity by neurtrophin-3.","volume":"2","author":"Ernfors","year":"1996","journal-title":"Nat. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1164\/rccm.200812-1845PP","article-title":"Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations.","volume":"180","author":"Flume","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.jcf.2015.06.005","article-title":"D-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models.","volume":"15","author":"Fox","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2017.00009","article-title":"The role of glia in the peripheral and central auditory system following noise overexposure: contribution to TNF-\u03b1 and IL-1\u03b2 to the pathogenesis of hearing loss.","volume":"11","author":"Fuentes-Santamar\u00eda","year":"2017","journal-title":"Front. Neuroanat."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.heares.2019\/01.022","article-title":"Residual inhibition: from the putative mechanisms to potential tinnitus treatment.","volume":"375","author":"Galazyuk","year":"2019","journal-title":"Hear. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jcf.2020.07.001","article-title":"Prospective cohort study of ototoxicity in persons with cystic fibrosis following a single course of intravenous tobramycin.","volume":"20","author":"Garinis","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"B33","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.jcf.2017.01.006","article-title":"The cumulative effects of intravenous antibiotic treatments on hearing in patients with cystic fibrosis.","volume":"16","author":"Garinis","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00110","article-title":"Insult-induced adaptive plasticity of the auditory system.","volume":"9","author":"Gold","year":"2014","journal-title":"Front. Neurosci."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10090639","article-title":"Perpulse inhibition of the auditory startle reflex assessment as hallmark of brainstem sensorimotor gating mechanisms.","volume":"10","author":"G\u00f3mez-Nieto","year":"2020","journal-title":"Brain Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/j.1365-2125.2011.03991.x","article-title":"Neurotoxic effects associated with antibiotic use: management considerations.","volume":"73","author":"Grill","year":"2011","journal-title":"Br. J. Clin. Phamacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.jneumeth.2015.07.001","article-title":"An improved approach to separating startle data from noise.","volume":"253","author":"Grimsley","year":"2015","journal-title":"J. Neurosci. Methods"},{"key":"B38","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j\/jcf.2020.02.014","article-title":"Ebselen attenuates tobramycin-induced ototoxicity in mice.","volume":"20","author":"Gu","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"B39","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.heares.2019.01.018","article-title":"Reliability and interrelations of seven proxy measures of cochlear synaptopathy.","volume":"375","author":"Guest","year":"2019","journal-title":"Hear. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1080\/14992027.2018.1455114","article-title":"Protection for medication-induced hearing loss: the state of the science.","volume":"57","author":"Hammill","year":"2018","journal-title":"Int. J. Audiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.jcf.2020.11.020","article-title":"Ototoxicity in cystic fibrosis patients receiving intravenous tobramycin for acute pulmonary exacerbation: ototoxicity following tobramycin treatment.","volume":"20","author":"Harruff","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1152\/physrev.00029.2020","article-title":"What\u2019s the buzz? The neuroscience and the treatment of tinnitus.","volume":"101","author":"Henton","year":"2021","journal-title":"Physiol. Rev."},{"key":"B43","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.heares.2019.01.006","article-title":"The role of monocytes and macrophages in the dynamic permeability of the blood-perilymph barrier.","volume":"374","author":"Hirose","year":"2019","journal-title":"Hear. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"65","DOI":"10.5588\/ijtld.19.0062","article-title":"Risk of hearing loss among multidrug-resistant tuberculosis patients according to cumulative aminoglycoside dose.","volume":"24","author":"Hong","year":"2020","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3989201","article-title":"N-methyl-D-Aspartate receptors involvement in the gentamicin-induced hearing loss and pathological changes of ribbon synapse in the mouse cochlear inner hair cells.","volume":"2018","author":"Hong","year":"2018","journal-title":"Neural Plast"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/937861","article-title":"Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection.","volume":"2011","author":"Huth","year":"2011","journal-title":"Int. J. Otolaryngol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.598406","article-title":"Acute and long-term circuit-level effects in the auditory cortex after sound trauma.","volume":"14","author":"Jeschke","year":"2021","journal-title":"Front. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00308","article-title":"Aminoglycoside-induced cochleotoxicity: a review.","volume":"11","author":"Jiang","year":"","journal-title":"Front. Cell. Neurosci."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00362","article-title":"Potential mechanisms underlying inflammation-enhanced aminoglycoside-induced cochleotoxicity.","volume":"11","author":"Jiang","year":"","journal-title":"Front. Cell. Neurosci."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00192","article-title":"Resolution of cochlear inflammation: novel target for preventing or ameliorating drug-, noise-, and age-related hearing loss.","volume":"11","author":"Kalinec","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2021.108209","article-title":"Development of ebselen for the treatment of sensorineural hearing loss and tinnitus.","volume":"108209","author":"Kil","year":"2021","journal-title":"Hear. Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/S1474-4422(13)70160-1","article-title":"Tinnitus: causes and clinical management.","volume":"12","author":"Langguth","year":"2013","journal-title":"Lancet Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0378-5955(91)90036-9","article-title":"Reduction and recovery of neuronal size in the cochlear nucleus of the chicken following aminoglycoside intoxication.","volume":"51","author":"Lippe","year":"1991","journal-title":"Hear. Res."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00060","article-title":"Cellular differences in the cochlea of CBA and B6 mice may underlie their difference in susceptibility to hearing loss.","volume":"13","author":"Liu","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1007\/s12035-014-8951-y","article-title":"Spontaneous and partial repair of ribbon synapse in cochlear inner hair cells after ototoxic withdrawal.","volume":"52","author":"Liu","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"16141","DOI":"10.1523\/JNEUROSCI.2499-12.2012","article-title":"Diminished cortical inhibition in an aging mouse model of chronic tinnitus.","volume":"32","author":"Llano","year":"2012","journal-title":"J. Neurosci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s10162-011-0276-1","article-title":"Development of tinnitus in CBA\/CaJ mice following sound exposure.","volume":"12","author":"Longenecker","year":"2011","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.brainres.2012.02.067","article-title":"Methodological optimization of tinnitus assessment using prepulse inhibition of the acoustic startle reflex.","volume":"1485","author":"Longenecker","year":"2012","journal-title":"Brain Res."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00207","article-title":"Variable effects of acoustic trauma on behavioral and neural correlates of tinnitus in individual animals.","volume":"10","author":"Longenecker","year":"2016","journal-title":"Front. Behav. Neurosci."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.561185","article-title":"A novel mouse model of aminoglycoside-induced hyperacusis and tinnitus.","volume":"14","author":"Longenecker","year":"2020","journal-title":"Front. Neurosci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.heares.2018.03.013","article-title":"Addressing variability in the acoustic startle reflex for accurate gap detection assessment.","volume":"363","author":"Longenecker","year":"2018","journal-title":"Hear. Res."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2020.107957","article-title":"Acoustic trauma induced the alteration of the activity balance of excitatory and inhibitory neurons in the inferior colliculus of mice.","volume":"391","author":"Ma","year":"2020","journal-title":"Hear. Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.heares.2005.10.003","article-title":"Spontaneous activity in the inferior colliculus of CBA\/J mice after manipulations that induce tinnitus.","volume":"212","author":"Ma","year":"2006","journal-title":"Hear. Res."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal3175","article-title":"Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans.","volume":"10","author":"Marks","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77754-z","article-title":"Ventral cochlear nucleus bushy cells encode hyperacusis in guinea pigs.","volume":"10","author":"Martel","year":"2020","journal-title":"Sci. Rep."},{"key":"B66","doi-asserted-by":"publisher","first-page":"21198","DOI":"10.1073\/pnas.1914088116","article-title":"Amyloid-beta impairs TOM1-mediated IL-1R1 signaling.","volume":"116","author":"Martini","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B67","doi-asserted-by":"publisher","first-page":"3577","DOI":"10.1172\/JCI68480","article-title":"Inner ear supporting cells protect hair cells by secreting HSP70.","volume":"123","author":"May","year":"2013","journal-title":"J. Clin. Invest."},{"key":"B68","doi-asserted-by":"publisher","first-page":"7601","DOI":"10.1073\/pnas.1100223108","article-title":"Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition.","volume":"108","author":"Middleton","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1038\/cdd.2015.48","article-title":"Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death.","volume":"22","author":"Monzack","year":"2015","journal-title":"Cell Death Differ."},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2019.107870","article-title":"Intravenously delivered aminoglycoside antibiotics, tobramycin and amikacin, are not ototoxic in mice.","volume":"386","author":"Ogier","year":"2020","journal-title":"Hear. Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"32423","DOI":"10.1073\/pnas.2013065117","article-title":"Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes.","volume":"117","author":"O\u2019Sullivan","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B72","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s10162-015-0519-7","article-title":"A chromosome 17 locus engenders frequency-specific non-progressive hearing loss that contributes to age-related hearing loss in mice.","volume":"16","author":"Peguero","year":"2015","journal-title":"JARO"},{"key":"B73","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1044\/2014_AJA-13-0037","article-title":"A review of hyperacusis and future directions: part II. Measurement, mechanisms, and treatment.","volume":"23","author":"Pienkowski","year":"2014","journal-title":"Am. J. Audiol."},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2013.00103","article-title":"Longterm-habituation of the startle response in mice is stimulus modality, but not context specific.","volume":"7","author":"Pilz","year":"2014","journal-title":"Front. Integr. Neurosci."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/life11020087","article-title":"Decreased sound tolerance in tinnitus patients.","volume":"11","author":"Raj-Koziak","year":"2021","journal-title":"Life"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.627522","article-title":"Co-occurrence of hyperacusis accelerates with tinnitus burden over time and requires medical care.","volume":"12","author":"Refat","year":"2021","journal-title":"Front. Neurol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.4103\/0028-3886.246258","article-title":"Neurotoxicity of the antibiotics: a comprehensive study.","volume":"66","author":"Rezaei","year":"2018","journal-title":"Neurol. India"},{"key":"B78","doi-asserted-by":"publisher","first-page":"14972","DOI":"10.1523\/JNEUROSCI.4028-10.2010","article-title":"Ringing ears: the neuroscience of tinnitus.","volume":"30","author":"Roberts","year":"2010","journal-title":"J. Neurosci."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroscience.2019.03.021","article-title":"Overview: hearing loss, tinnitus, hyperacusis, and the role of central gain.","volume":"407","author":"Roberts","year":"2019","journal-title":"Neurosci"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-05947-6","article-title":"Low-dose amikacin in the treatment of multidrug-resistant tuberculosis (MDR-TB).","volume":"21","author":"Sabur","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1044\/2020_AJA-20-00023","article-title":"Review: neural mechanisms of tinnitus and hyperacusis in acute drug-induced ototoxicity.","author":"Salvi","year":"2021","journal-title":"Am. J. Audiol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s10162-009-0198-3","article-title":"Expression of fractalkine receptor CX3CR1 on cochlear macrophages influences survival of hair cells following ototoxic injury.","volume":"11","author":"Sato","year":"2010","journal-title":"JARO"},{"key":"B83","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/s0006-8993(98)01123-8","article-title":"Aminoglycoside neurotoxicity involves NMDA receptor activation.","volume":"815","author":"Segal","year":"1999","journal-title":"Brain Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.1007\/s00213-020-05654-1","article-title":"A phase 2a randomized, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania.","volume":"237","author":"Sharpley","year":"2020","journal-title":"Psychopharmacology (Berl.)"},{"key":"B85","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.neuron.2019.05.008","article-title":"Mechanisms of noise-induced tinnitus: insights from cellular studies.","volume":"103","author":"Shore","year":"2019","journal-title":"Neuron"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001021.pub3","article-title":"Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis.","volume":"3","author":"Smith","year":"2018","journal-title":"Cochrane Database of Syst. Rev."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.01.003","article-title":"Re-evaluating aminoglycoside ototoxicity.","volume":"20","author":"Staecker","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00190","article-title":"Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis in sensory hair cells in the mouse inner ear.","volume":"9","author":"Tao","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2019.00055","article-title":"Evidence of hyperacusis in adult rats following non-traumatic sound exposure.","volume":"13","author":"Thomas","year":"2019","journal-title":"Front. Syst. Neurosci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1002\/jnr.22827","article-title":"Time course of tinnitus development following noise exposure.","volume":"90","author":"Turner","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1111\/j.1528-1157.1996.tb00549.x","article-title":"Seizures in lung transplant recipients.","volume":"37","author":"Vaughn","year":"1996","journal-title":"Epilepsia"},{"key":"B92","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.4155\/fmc-2019-0218","article-title":"Mechanisms of ebselen as a therapeutic and its pharmacology applications.","volume":"12","author":"Wang","year":"2020","journal-title":"Future Med. Chem."},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000307","article-title":"Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models.","volume":"17","author":"Wang","year":"2019","journal-title":"PLoS Biol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1044\/2020_AJA-20-00117","article-title":"Wideband acoustic reflex growth in adults with cystic fibrosis.","author":"Westman","year":"2021","journal-title":"Am. J. Audiol."},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00106","article-title":"The contribution of immune infiltrates to ototoxicity and cochlear hair cell loss.","volume":"11","author":"Wood","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8833087","article-title":"Noise exposure alters glutamatergic and GABAergic synaptic connectivity in the hippocampus and its relevance to tinnitus.","volume":"2021","author":"Zhang","year":"2021","journal-title":"Neural Plast."},{"key":"B97","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/s0378-5955(99)00003-9","article-title":"Assessment of hearing in 80 inbred strains of mice by ABR threshold analysis.","volume":"130","author":"Zheng","year":"1999","journal-title":"Hear. Res."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2021.715952\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:14:21Z","timestamp":1630714461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2021.715952\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,1]]},"references-count":97,"alternative-id":["10.3389\/fnmol.2021.715952"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2021.715952","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,1]]},"article-number":"715952"}}