Dataset Information

Intracochlear Perfusion of Tumor Necrosis Factor-Alpha Induces Sensorineural Hearing Loss and Synaptic Degeneration in Guinea Pigs.

ABSTRACT: Tumor necrosis factor-alpha (TNF-?) is a proinflammatory cytokine that plays a prominent role in the nervous system, mediating a range of physiologic and pathologic functions. In the auditory system, elevated levels of TNF-? have been implicated in several types of sensorineural hearing loss, including sensorineural hearing loss induced by vestibular schwannoma, a potentially fatal intracranial tumor that originates from the eighth cranial nerve; however, the mechanisms underlying the tumor's deleterious effects on hearing are not well-understood. Here, we investigated the effect of acute elevations of TNF-? in the inner ear on cochlear function and morphology by perfusing the cochlea with TNF-? in vivo in guinea pigs. TNF-? perfusion did not significantly change thresholds for compound action potential (CAP) responses, which reflect cochlear nerve activity, or distortion product otoacoustic emissions, which reflect outer hair cell integrity. However, intracochlear TNF-? perfusion reduced CAP amplitudes and increased the number of inner hair cell synapses without paired post-synaptic terminals, suggesting a pattern of synaptic degeneration that resembles that observed in primary cochlear neuropathy. Additionally, etanercept, a TNF-? blocker, protected against TNF-?-induced synaptopathy when administered systemically prior to intracochlear TNF-? perfusion. Findings motivate further investigation into the harmful effects of chronically elevated intracochlear levels of TNF-?, and the potential for etanercept to counter these effects.

SUBMITTER: Katsumi S

PROVIDER: S-EPMC7025643 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Intracochlear Perfusion of Tumor Necrosis Factor-Alpha Induces Sensorineural Hearing Loss and Synaptic Degeneration in Guinea Pigs.

Katsumi Sachiyo S Sahin Mehmet I MI Lewis Rebecca M RM Iyer Janani S JS Landegger Lukas D LD Stankovic Konstantina M KM

Frontiers in neurology 20200210

Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays a prominent role in the nervous system, mediating a range of physiologic and pathologic functions. In the auditory system, elevated levels of TNF-α have been implicated in several types of sensorineural hearing loss, including sensorineural hearing loss induced by vestibular schwannoma, a potentially fatal intracranial tumor that originates from the eighth cranial nerve; however, the mechanisms underlying the tumor's de ...[more]

PMID: 32116980

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Project description:IntroductionTo compare inpatient treated patients with idiopathic (ISSNHL) and non-idiopathic sudden sensorineural hearing loss (NISSNHL) regarding frequency, hearing loss, treatment and outcome.MethodsAll 574 inpatient patients (51% male, median age: 60 years) with ISSNHL and NISSNHL, who were treated in federal state Thuringia in 2011 and 2012, were included retrospectively. Univariate and multivariate statistical analyses were performed.ResultsISSNHL was diagnosed in 490 patients (85%), NISSNHL in 84 patients (15%). 49% of these cases had hearing loss due to acute otitis media, 37% through varicella-zoster infection or Lyme disease, 10% through Menière disease and 7% due to other reasons. Patients with ISSNHL and NISSNHL showed no difference between age, gender, side of hearing loss, presence of tinnitus or vertigo and their comorbidities. 45% of patients with ISSNHL and 62% with NISSNHL had an outpatient treatment prior to inpatient treatment (p < 0.001). The mean interval between onset of hearing loss to inpatient treatment was shorter in ISSNHL (7.7 days) than in NISSNHL (8.9 days; p = 0.02). The initial hearing loss of the three most affected frequencies in pure-tone average (3PTAmax) scaled 72.9 dBHL ± 31.3 dBHL in ISSNHL and 67.4 dBHL ± 30.5 dBHL in NISSNHL. In the case of acute otitis media, 3PTAmax (59.7 dBHL ± 24.6 dBHL) was lower than in the case of varicella-zoster infection or Lyme disease (80.11 dBHL ± 34.19 dBHL; p = 0.015). Mean absolute hearing gain (Δ3PTAmaxabs) was 8.1 dB ± 18.8 dB in patients with ISSNHL, and not different in NISSNHL patients with 10.2 dB ± 17.6 dB. A Δ3PTAmaxabs ≥ 10 dB was reached in 34.3% of the patients with ISSNHL and to a significantly higher rate of 48.8% in NISSNHL patients (p = 0.011).ConclusionsISSNHL and NISSNHL show no relevant baseline differences. ISSNHL tends to have a higher initial hearing loss. NISSHNL shows a better outcome than ISSNHL.

Dataset Information

Intracochlear Perfusion of Tumor Necrosis Factor-Alpha Induces Sensorineural Hearing Loss and Synaptic Degeneration in Guinea Pigs.

Publications

Intracochlear Perfusion of Tumor Necrosis Factor-Alpha Induces Sensorineural Hearing Loss and Synaptic Degeneration in Guinea Pigs.

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