Dexamethasone protects organ of corti explants against tumor necrosis factor-alpha–induced loss of auditory hair cells and alters the expression levels of apoptosis-related genes

Dinh, Christine T.; Haake, Scott M.; Chen, S.; Hoang, Kimberly; Nong, Eva; Eshraghi, Adrien A.; Bałkany, Thomas J.; Water, Thomas R. Van De

doi:10.1016/j.neuroscience.2008.09.012

Cited by 71 publications

(89 citation statements)

References 59 publications

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“…There is evidence that corticosteroid treatment can reduce the inflammatory response and protect against stress-induced programmed cell death within the cochlea [18,19,20]. Treatment with a corticosteroid can attenuate hearing loss from several different types of trauma to the inner ear such as: (1) noise exposure [21,22,23]; (2) vibration-induced trauma [24]; (3) aminoglycoside exposure [25,26]; (4) ischemia-reperfusion injury [27]; (5) hearing loss associated with bacterial meningitis [28]; (6) cochlear implant electrode insertion trauma (EIT)-induced hearing loss [29,30].…”

Section: Corticosteroidsmentioning

confidence: 99%

“…Our laboratory group at the University of Miami Ear Institute has evaluated the otoprotective effects of DXMb (this form of the drug can be incorporated into polymers for biorelease) on organ of Corti explants exposed to TNFα, a pro-inflammatory cytokine that is capable of initiating programmed cell death of auditory hair cells in vitro [19]. Organ of Corti explants from 3-day-old rats were cultured in either: (1) control media, i.e.…”

Section: Corticosteroidsmentioning

confidence: 99%

“…In addition, it also initiated upregulation of anti-apoptotic genes Bcl-2 and Bcl-xl as well as a decrease in the Bax/Bcl-2 ratio (fig. 1) [19]. This pattern of gene expression is suggestive of possible NFĸB involvement; therefore, further studies evaluating phosphorylated NFĸB (p-NFĸB) were performed.…”

Section: Corticosteroidsmentioning

confidence: 99%

“…c TNFα (2 µg/ml)-exposed + DXMb (70 µg/ml)-treated explant showing a normal pattern of IHCs and OHCs. Figure reproduced with permission from Dinh et al [19]. …”

Section: Corticosteroidsmentioning

confidence: 99%

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Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Dinh

Water²

2009

Audiol Neurotol

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The programmed cell death of stress-damaged auditory hair cells can occur through a variety of signal pathways, and therapeutic modalities that block pro-cell-death pathways are being developed and evaluated for hearing preservation. Because of their ability to have both anti-inflammatory and anti-apoptotic actions, corticosteroids have long been used to protect against several types of acute sensorineural hearing loss. Other anti-apoptotic drugs that target the mitogen-activated protein kinase (MAPK)/c-Jun-N terminal kinase (JNK) signal cascade, such as D-JNKI-1 (AM-111) and SP600125, have produced promising results both in vitro and in laboratory animal studies, with AM-111 showing promise in preliminary clinical trials. Antioxidant drugs, e.g. sodium thiosulfate, N-acetylcysteine, and D-methionine, have been shown in animal studies to attenuate permanent threshold shifts in hearing by reducing oxidative stress. In addition to reviewing selected therapeutic trends for the conservation of hearing, we review our experiences with dexamethasone and D-JNKI-1 and report results from our current research.

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Section: Corticosteroidsmentioning

confidence: 99%

Section: Corticosteroidsmentioning

confidence: 99%

Section: Corticosteroidsmentioning

confidence: 99%

“…c TNFα (2 µg/ml)-exposed + DXMb (70 µg/ml)-treated explant showing a normal pattern of IHCs and OHCs. Figure reproduced with permission from Dinh et al [19]. …”

Section: Corticosteroidsmentioning

confidence: 99%

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Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Dinh

Water²

2009

Audiol Neurotol

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“…Among the pro‐inflammatory cytokines, tumor necrosis factor‐alpha (TNF‐α) has been shown to play a role in the loss of cochlear sensory hair cells in animal models (Demirhan et al ., 2013) and to contribute to sensorineural hearing loss in humans (Svrakic et al ., 2012). Specifically, exogenous TNF‐α induced loss of hair cells in rat Organ of Corti explants and this TNF‐α‐induced ototoxicity involved the upregulation of a series of apoptosis‐related genes (Dinh et al ., 2008). Elevated levels of TNF‐α have been detected in inner ears after exposure to noise (Fujioka et al ., 2006) and ototoxic medications (Park et al ., 2012).…”

Section: Introductionmentioning

confidence: 99%

Activation of TRAIL‐DR5 pathway promotes sensorineural degeneration in the inner ear

et al. 2016

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SummaryTumor necrosis factor (TNF) family cytokines are important mediators of inflammation. Elevated levels of serum TNF‐α are associated with human sensorineural hearing loss via poorly understood mechanisms. We demonstrate, for the first time, expression of TNF‐related apoptosis‐inducing ligand (TRAIL) and its signaling death receptor 5 (DR5) in the murine inner ear and show that exogenous TRAIL can trigger hair cell and neuronal degeneration, which can be partly prevented with DR5‐blocking antibodies.

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Dexamethasone (DXM)‐Coated Poly(lactic‐co‐glycolic acid) (PLGA) Microneedles as an Improved Drug Delivery System for Intracochlear Biodegradable Devices

Pawley

Goncalves

Bas

et al. 2021

Advanced Therapeutics

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Uniform drug delivery techniques are challenging to develop for the inner ear due to the complexity of the cochlear anatomy. A promising solution is the use of biodegradable polymers because the continuous release of therapeutics without introducing toxic compounds is desirable. Using a microneedle approach lends the polymeric microneedle the capability to be placed inside of the scala tympani, releasing drugs overtime. Poly(lactic-co-glycolic acid) (PLGA) microneedles is prepared by dissolving dimethyl sulfoxide with either a) Rhodamine B, to study the drug release profile in vitro, b) FM1-43, to study the drug release profile in vivo, or c) dexamethasone (DXM), to protect hair cell (HC) loss in vivo. The Rhodamine B studies show that the dye begins release from the microneedles within 30 min. The ototoxicity assessment of the DXM-coated microneedles in vitro shows a significant reduction of HC losses when compared to control microneedles in an ototoxic environment. In vivo data show reduced hearing threshold for animals treated with DXM-infused microneedles, providing a proof of concept of the methodology developed. Drug-infused polymeric microneedles provide a promising method to deliver DXM to the inner ear over controlled periods of time protecting hair cells, thus minimizing hearing loss (HL).

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Dexamethasone protects organ of corti explants against tumor necrosis factor-alpha–induced loss of auditory hair cells and alters the expression levels of apoptosis-related genes

Cited by 71 publications

References 59 publications

Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Activation of TRAIL‐DR5 pathway promotes sensorineural degeneration in the inner ear

Dexamethasone (DXM)‐Coated Poly(lactic‐co‐glycolic acid) (PLGA) Microneedles as an Improved Drug Delivery System for Intracochlear Biodegradable Devices

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