Vestibular damage in chronic ototoxicity: A mini-review

Abstract

Ototoxicity is a major cause of the loss of hearing and balance in humans. Ototoxic compounds include pharmaceuticals such as aminoglycoside antibiotics, anti-malarial drugs, loop diuretics and chemotherapeutic platinum agents, and industrial chemicals including several solvents and nitriles. Human and rodent data indicate that the main target of toxicity is hair cells (HCs), which are the mechanosensory cells responsible for sensory transduction in both the auditory and the vestibular system. Nevertheless, the compounds may also affect the auditory and vestibular ganglion neurons. Exposure to ototoxic compounds has been found to cause HC apoptosis, HC necrosis, and damage to the afferent terminals, of differing severity depending on the ototoxicity model. One major pathway frequently involved in HC apoptosis is the c-jun N-terminal kinase (JNK) signaling pathway activated by reactive oxygen species, but other apoptotic pathways can also play a role in ototoxicity. Moreover, little is known about the effects of chronic low-dose exposure. In rodent vestibular epithelia, extrusion of live HCs from the sensory epithelium may be the predominant form of cell demise during chronic ototoxicity. In addition, greater involvement of the afferent terminals may occur, particularly the calyx units contacting type I vestibular HCs. As glutamate is the neurotransmitter in this synapse, excitotoxic phenomena may participate in afferent and ganglion neuron damage. Better knowledge of the events that take place in chronic ototoxicity is of great interest, as it will increase understanding of the sensory loss associated with chronic exposure and aging.

Hearing loss and falls: A systematic review and meta‐analysis

“…Several potential mechanisms could explain the association between hearing loss and falls. First, the vestibular system lies in close anatomic proximity to the cochlea, and certain exposures such as infections (e.g., mumps, varicella zoster) and ototoxic medications (e.g., aminoglycosides) target hair cells in both the cochlea and vestibular system . Moreover, the aging process is known to impact both the cochlear and vestibular systems .…”

Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms

“…Classic studies of aminoglycoside ototoxicity focused on the hair cells as primary targets and considered neural losses to be a secondary consequence of hair cell loss (McFadden et al., 2004; Takeno et al, 1998; Bae et al, 2008; Dodson and Mohuiddin, 2000). However, aminoglycoside-induced excitotoxic swelling of nerve terminals also has been reported in both cochlear and vestibular end organs (Basile et al, 1996; Duan et al, 2000; Sedo-Cabezon et al, 2014; Smith, 1999), suggesting direct, excitotoxic effects of these drugs on neural elements.…”

Development and regeneration of vestibular hair cells in mammals

“…Hair cells appear to be one of the more susceptible vestibular cell types; however, loss of vestibular ganglion neurons and damage to supporting cells has also been observed [52, 96, 97]. For example, chronic exposure to 3,3′-iminodipropionitrile can lead to transient disassembly of calyceal synapses in the absence of any overt hair cell or ganglion damage [98].…”