The Injured Cochlea as a Target for Inflammatory Processes, Initiation of Cell Death Pathways and Application of Related Otoprotective Strategies

Abstract

One of the causes of sensorineural hearing loss is the loss of auditory hair cells following exposure to environmental stresses. Auditory hair cell death in response to cochlear trauma occurs via both necrosis and apoptosis. Apoptosis of hair cells involves the caspase and MAPK/JNK pathways which are activated by oxidative stress and secretion of inflammatory cytokines in response to trauma. Identification of the pathways that lead to apoptosis provides therapeutic targets for the conservation of hearing. Antioxidants reduce the level of reactive oxygen species and reactive nitrogen species generated by oxidative stress in response to acoustic trauma, aminoglycoside and platinum-based drugs. Caspase inhibitors affect both the extrinsic and intrinsic apoptotic pathways thereby reducing cisplatin, aminoglycoside, hydraulic trauma and ischemia-induced hearing losses. Corticosteroid therapy reduces inflammation and inhibits apoptosis while activating pro-survival pathways in the organ of Corti following exposure to noise, vibration, cisplatin, aminoglycoside, ischemia/reperfusion injury, bacterial meningitis and electrode insertion trauma. Inhibitors of JNK signaling pathway prevent apoptosis of auditory hair cells following electrode insertion trauma, acute labyrinthitis, acoustic trauma and aminoglycoside ototoxicity. This review provides an overview of the different pathways involved in auditory hair cell death following an environmental stress and both traditional and newly developed drugs that are currently being studied or used for the treatment of acute hearing loss. Recent patents related to otoprotective strategies to conserve hearing and auditory hair cells are also discussed in this review.

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

“…In the context of our current study, similar as other aminoglycosides, gentamicin is found to accumulate in the mitochondria of hair cells and cause excessive production of reactive oxygen species 26, which is likely to be the cause of aminoglycoside‐induced hearing loss 27. Indeed, early reports suggested that gentamicin‐induced oxidative stress, and in turn apoptosis in hair cells of various species 28, 29, 30.…”

Assessment of Nutrient Supplement to Reduce Gentamicin-Induced Ototoxicity

“…The data presented here build on a compelling literature documenting the role of oxidative stress in acquired hearing loss, and demonstrate the benefit of free radical scavengers. There is an important role of free radical formation in hearing loss after cisplatin (Cheng et al 2005;Dehne et al 2001;Devarajan et al 2002) and noise (for reviews, see Le Prell and Bao 2011; Abi-Hachem et al 2010;Poirrier et al 2010;Henderson et al 2006;Le Prell et al 2007b). Oxidative stress has also been implicated in age-related hearing loss (ARHL; Seidman 2000; Le and Keithley 2007;Jiang et al 2007).…”

“…A variety of investigations into antioxidant defense against gentamicin insult and other aminoglycosides have been encouraging (for reviews, see Xie et al 2011;Rybak and Kelly 2003;Rybak and Whitworth 2005;Abi-Hachem et al 2010;Poirrier et al 2010;Campbell and Le Prell 2012). There are now a variety of drugs and other substances that have been shown to effectively attenuate cell death and hearing loss after gentamicin insult, although complete protection has been elusive (for summary, see Table 1).…”

Potential protective effect of N-acetyl cysteine in acoustic trauma: An experimental study using scanning electron microscopy

“…[1][2][3] These findings suggest that antioxidants have the potential to block molecular cascades that are triggered by auditory trauma, which induces oxidative stress and results in permanent threshold shifts (PTS) and hearing loss. 4 In blast-exposed ears, cochlear pathology includes scar formation replacing dead hair cells, fused and damaged stereocilia, and in some extreme cases, separation of the organ of Corti from the basilar membrane.…”