Conservation of Hearing and Protection of Auditory Hair Cells against Trauma-Induced Losses by Local Dexamethasone Therapy: Molecular and Genetic Mechanisms

Water, Thomas R. Van De; Hachem, Ralph N Abi; Dinh, Christine T.; Bas, Esperanza; Haake, Scott M.; Hoosien, Gia; Vivero, Richard J.; Chan, Sherry; He, Jao; Eshraghi, Adrien A.; Angeli, Simón I.; Telischi, Fred F.; Bałkany, Thomas J.

doi:10.1179/146701010x12671178390834

Cited by 39 publications

(34 citation statements)

References 29 publications

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“…Some variables can be improved upon, such as surgical trauma, implant size, and surgical approach. There are other factors, however, that, at present, cannot be clinically modified for human subjects such as individual inflammatory response and cellular apoptosis (11,15,16).…”

mentioning

confidence: 97%

Impact of Intrascalar Electrode Location, Electrode Type, and Angular Insertion Depth on Residual Hearing in Cochlear Implant Patients

Wanna¹,

Noble²,

Gifford³

et al. 2015

Otology &Amp; Neurotology

107

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mentioning

confidence: 97%

Impact of Intrascalar Electrode Location, Electrode Type, and Angular Insertion Depth on Residual Hearing in Cochlear Implant Patients

Wanna¹,

Noble²,

Gifford³

et al. 2015

Otology &Amp; Neurotology

107

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“…The activation of caspase-3 was also seen in the UB-OC1 auditory cell line undergoing apoptosis following treatment with TNF-α (Park et al 2012). Conversely, co-treatment with dexamethasone rescued TNF-α-induced apoptosis by down-regulating pro-apoptotic genes such as TNF receptor 1 (Van De Water et al 2010). TNF-α has also been suggested to play a role in ischemic hearing loss, as TNF-α treatment reduced both cochlear blood flow and capillary diameter in spiral ligament capillaries and spiral modiolar arteries of guinea pigs (Scherer et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Tumor Necrosis Factor-alpha-mutant Mice Exhibit High Frequency Hearing Loss

Oishi

Zheng

Hill

et al. 2013

JARO

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Exogenous tumor necrosis factor-alpha (TNF-α) plays a role in auditory hair cell death by altering the expression of apoptosis-related genes in response to noxious stimuli. Little is known, however, about the function of TNF-α in normal hair cell physiology. We, therefore, investigated the cochlear morphology and auditory function of TNF-α-deficient mice. Auditory evoked brainstem response showed significantly higher thresholds, especially at higher frequencies, in 1-month-old TNF-α −/− mice as compared to TNF-α +/− and wild type (WT); hearing loss did not progress further from 1 to 4 months of age. There was no difference in the gross morphology of the organ of Corti, lateral wall, and spiral ganglion cells in TNF-α −/− mice compared to WT mice at 4 months of age, nor were there differences in the anatomy of the auditory ossicles. Outer hair cells were completely intact in surface preparations of the organ of Corti of TNF-α −/− mice, and synaptic ribbon counts of TNF-α −/− and WT mice at 4 months of age were similar. Reduced amplitudes of distortion product otoacoustic emissions, however, indicated dysfunction of outer hair cells in TNF-α −/− mice. Scanning electron microscopy revealed that stereocilia were sporadically absent in the basal turn and distorted in the middle turn. In summary, our results demonstrate that TNF-α-mutant mice exhibit early hearing loss, especially at higher frequencies, and that loss or malformation of the stereocilia of outer hair cells appears to be a contributing factor.

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“…It is not possible to distinguish between these, as they proceed in concert and could potentially influence each other. Early after implantation, injury signalling is thought to lead to local production of inflammatory cytokines that attract immune-competent cells to the surgical site [Yamamoto et al, 2009;van De Water et al, 2010;Bas et al, 2012]. These are initially endogenous to the cochlea [Shi, 2010], but will also be recruited from the circulation after up-regulation of cell adhesion molecules, such as I-CAM1, on the endothelium of cochlear venules [Suzuki and Harris, 1995;Tornabene et al, 2006].…”

Section: Biological Response Of the Cochlea To Implantation And Steroidsmentioning

confidence: 99%

“…In experimental cochlear implantation, glucocorticosteroids applied locally to the cochlea act through anti-inflammatory, anti-apoptotic and antioxidant pathways, with direct effects upon the IHCs and OHCs observed [Dinh et al, 2008a, b;Haake et al, 2009;van De Water et al, 2010;Eshraghi et al, 2011]. Systemically administered glucocorticosteroids also act at the cochlear level [Connolly et al, 2011] but in addition are thought to reduce the activation of circulating immunecompetent cells [Souter et al, 2012].…”

Section: Biological Response Of the Cochlea To Implantation And Steroidsmentioning

confidence: 99%

Effect of Both Local and Systemically Administered Dexamethasone on Long-Term Hearing and Tissue Response in a Guinea Pig Model of Cochlear Implantation

et al. 2013

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Dexamethasone administered prior to cochlear implantation has been shown to reduce the loss of residual hearing in experimental settings. However, its effect on the tissue response around the implant has not been extensively studied. In this study dexamethasone sodium phosphate was administered to guinea pigs via local delivery to the round window (2% dexamethasone for 120 min prior to surgery, ‘local 2/120', or 20% dexamethasone for 30 min prior to surgery) or intravenously (2 mg/kg dexamethasone for 60 min) prior to implantation. Auditory brainstem responses (ABR) were monitored for 3 months, after which the cochleae were embedded in Spurr's resin and sectioned. The extent of the tissue response and the survival of the neurosensory structures were analysed. Both local 2/120 and systemically delivered dexamethasone improved ABR thresholds when compared with control animals. Systemic dexamethasone also reduced the tissue response around the electrode. This suggests that whilst both locally and systemically administered dexamethasone can protect residual hearing after cochlear implantation, their effects upon the tissue response to implantation may differ.

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Conservation of Hearing and Protection of Auditory Hair Cells against Trauma-Induced Losses by Local Dexamethasone Therapy: Molecular and Genetic Mechanisms

Abstract: DXM exert its otoprotective action by activation of cell signal molecules (e.g., NFkB) that alter the expression of anti- and pro-apoptosis genes.

Cited by 39 publications

References 29 publications

Impact of Intrascalar Electrode Location, Electrode Type, and Angular Insertion Depth on Residual Hearing in Cochlear Implant Patients

Impact of Intrascalar Electrode Location, Electrode Type, and Angular Insertion Depth on Residual Hearing in Cochlear Implant Patients

Tumor Necrosis Factor-alpha-mutant Mice Exhibit High Frequency Hearing Loss

Effect of Both Local and Systemically Administered Dexamethasone on Long-Term Hearing and Tissue Response in a Guinea Pig Model of Cochlear Implantation

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