Electrical Stimulation Degenerated Cochlear Synapses Through Oxidative Stress in Neonatal Cochlear Explants

Liang, Qiong; Shen, Na; Lai, Bin; Xu, Changjian; Sun, Zengjun; Wang, Zhengmin; Li, Shufeng

doi:10.3389/fnins.2019.01073

Cited by 12 publications

(14 citation statements)

References 40 publications

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“…Mitochondria (Bullen et al 2015 ), which are more commonly located at the base of the hair cells in the vicinity of the ribbon synapses, could release more reactive oxygen species, thereby damaging the synapses. This assumption is corroborated by a recent study where a pharmacological upregulation of endogenous antioxidative enzymes was able to rescue changes induced by electrical stimulation (Liang et al 2019 ). Labelling of the postsynaptic receptors would have been helpful in assessing damage to synaptic signalling.…”

Section: Discussionsupporting

confidence: 65%

“…The present study provides initial evidence that in vitro oxidative stress could be triggered by electrical stimulation and that the anti-inflammatory and radical scavenging substance dexamethasone can be partially protective. Indeed, a recent study showed that electrical stimulation increased ROS and reactive nitrogen species leading to loss of peripheral spiral ganglion neuron fibres (Liang et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

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Differential Effects of Low- and High-Dose Dexamethasone on Electrically Induced Damage of the Cultured Organ of Corti

et al. 2020

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An increased number of patients with residual hearing are undergoing cochlear implantation. A subset of these experience delayed hearing loss post-implantation, and the aetiology of this loss is not well understood. Our previous studies suggest that electrical stimulation can induce damage to hair cells in organ of Corti (OC) organotypic cultures. Dexamethasone has the potential to protect residual hearing due to its multiple effects on cells and tissue (e.g., anti-inflammatory, free radical scavenger). We therefore hypothesized that dexamethasone treatment could prevent electrical stimulation induced changes in the OC. Organ of Corti explants from neonatal rats (P2–4) were cultured for 24 h with two different concentrations of dexamethasone. Thereafter, OC were subjected to a charge-balanced biphasic pulsed electrical stimulation (0.44–2 mA) for a further 24 h. Unstimulated dexamethasone-treated OC served as controls. Outcome analysis included immunohistochemical labelling of ribbon synapses, histochemical analysis of free reactive oxygen species and morphological analysis of stereocilia bundles. Overall, the protective effects of dexamethasone on electrically induced damage in cochlear explants were moderate. High-dose dexamethasone protected bundle integrity at higher current levels. Low-dose dexamethasone tended to increase ribbon density in the apical region.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Differential Effects of Low- and High-Dose Dexamethasone on Electrically Induced Damage of the Cultured Organ of Corti

et al. 2020

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“…Pharmacological up-regulation of GPx1 [ 23 ] as induced by ebselen has been shown to prevent noise-induced hearing loss both in animal models as well in clinical trials [ 24 ]. On a cellular level, GPx1 up-regulation in the cochlea protects inner hair cells from denervation, prevents swelling of the afferent dendrites and of the stria vascularis and is regarded as an endogenous protective mechanism of the cochlea [ 23 , 25 , 26 ]. In obese patients with an unhealthy metabolic profile and at an increased risk to develop cardiovascular disease, SBP1 levels are reduced when compared to obese patients with a healthy metabolic profile [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Proteome profile of patients with excellent and poor speech intelligibility after cochlear implantation: Can perilymph proteins predict performance?

et al. 2022

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Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea microenvironment. In order to clarify whether the protein composition of the perilymph can provide new insights into individual hearing performance after cochlear implantation (CI), computational analysis in correlation to clinical performance after CI were performed based on the proteome profile derived from perilymph samples (liquid biopsies). Perilymph samples from cochlear implant recipients have been analyzed by mass spectrometry (MS). The proteins were identified using the shot-gun proteomics method and quantified and analyzed using Max Quant, Perseus and IPA software. A total of 75 perilymph samples from 68 (adults and children) patients were included in the analysis. Speech perception data one year after implantation were available for 45 patients and these were used for subsequent analysis. According to their hearing performance, patients with excellent (n = 22) and poor (n = 14) performance one year after CI were identified and used for further analysis. The protein composition and statistically significant differences in the two groups were detected by relative quantification of the perilymph proteins. With this procedure, a selection of 287 proteins were identified in at least eight samples in both groups. In the perilymph of the patients with excellent and poor performance, five and six significantly elevated proteins were identified respectively. These proteins seem to be involved in different immunological processes in excellent and poor performer. Further analysis on the role of specific proteins as predictors for poor or excellent performance among CI recipients are mandatory. Combinatory analysis of molecular inner ear profiles and clinical performance data using bioinformatics analysis may open up new possibilities for patient stratification. The impact of such prediction algorithms on diagnosis and treatment needs to be established in further studies.

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“…In addition to hair cells and ribbon synapses, these neurons play an important role in normal hearing. 5 In addition, anesthetic exposure during pregnancy may cause postsynaptic changes in the offspring mice during development. 31 Further study is warranted to test the postsynaptic change of the ribbon synapses.…”

Section: Discussionmentioning

confidence: 99%

“…Normal hearing requires accurate sound conduction to the central nervous system and accurate signal coding. Drug ototoxicity is a main cause of sensorineural hearing loss, often through the loss of hair cells, 3,4 degeneration of spiral ganglion nerves, 5 or damage to ribbon synapses. 6 Ribbon synapses, located between inner hair cells and spiral ganglion neurons, are considered crucial for maintaining normal hearing function.…”

Section: Introductionmentioning

confidence: 99%

<p>Ribbon Synapses and Hearing Impairment in Mice After in utero Sevoflurane Exposure</p>

Yuan¹,

Liu²,

Li³

et al. 2020

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Introduction In utero, exposure to sevoflurane (a commonly used inhalation anesthetic) can lead to hearing impairment in offspring mice, but the underlying impairment mechanism is not known. Materials and Methods Day-15 pregnant mice were treated with 2.5% sevoflurane for 2 h to investigate sevoflurane ototoxicity. Cochleae from offspring mice were harvested for hair-cell and ribbon-synapse assessments. Hearing in offspring mice was assessed at postnatal day 30 using an auditory brainstem-response (ABR) test. Cochlear-explant cultures from offspring mice were exposed to 2.5% sevoflurane for 6 h. Immediately after treatment, explants were assessed for hair-cell morphology, mitochondrial oxidative stress, and autophagy. Results In utero, sevoflurane exposure impaired hearing in the offspring is demonstrated by a decrease in ABR wave I amplitudes, a marker for ribbon-synapse functionality. Sevoflurane exposure caused no obvious damage to hair cells, but cochlear ribbon synapses were reduced in postnatal day 15 offspring, and partially recovered by postnatal day 30. Sevoflurane treatment also increased mitochondrial reactive-oxygen species stress and decreased autophagy in the cochlear explants. Conclusion These results suggest that oxidative stress and reduced autophagy may underly ribbon-synapse involvement in sevoflurane-induced hearing loss.

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Electrical Stimulation Degenerated Cochlear Synapses Through Oxidative Stress in Neonatal Cochlear Explants

Cited by 12 publications

References 40 publications

Differential Effects of Low- and High-Dose Dexamethasone on Electrically Induced Damage of the Cultured Organ of Corti

Differential Effects of Low- and High-Dose Dexamethasone on Electrically Induced Damage of the Cultured Organ of Corti

Proteome profile of patients with excellent and poor speech intelligibility after cochlear implantation: Can perilymph proteins predict performance?

<p>Ribbon Synapses and Hearing Impairment in Mice After in utero Sevoflurane Exposure</p>

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