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Abstract

This study investigates the morphological and molecular changes that occur in the inner hair cell area of the rat cochlea following aminoglycoside treatment. Rats were injected daily with 500 mg/kg of amikacin between postnatal day 9 (PND9) and PND16. Cochleae were examined at PND16 to PND120 using both scanning and transmission electron microscopy and molecular fluorescent labeling. The inner hair cells showed obvious signs of apoptosis in response to amikacin treatment and most of them were missing by one week after the end of the aminoglycoside exposure period. Concomitantly, the epithelium became scarred as the surrounding supporting cells expanded and filled the space vacated by the missing IHCs. The mid-basolateral region of these modified supporting cells was surrounded by many afferent and efferent terminals. However, these cells expressed neither calbindin nor SNAP25, proteins that are both expressed by IHCs in the normal, untreated organ of Corti in the rat. In addition, these supporting cells remained attached to the basal lamina by a thin cytoplasmic process. The supporting cells surrounding the inner hair cells therefore appear unable to convert directly into inner hair cells following aminoglycoside induced hair-cell loss but may be able to provide trophic support for the remaining afferent and efferent neurites.

Pathomorphological peculiarities of damage to hair cells of the organ of Corti in experimental sensorineural hearing loss

“…3, d, e). These changes can be seen after treatment with aminoglycosides, cisplatin, under conditions of chronic renal insufficiency, and chronic noise exposure [2][3][4][5]8,9,11,13]. This process is asynchronous in neighboring cells, which fact explains the presence of just solitary apoptosis figures in tissues (in contrast to necrosis).…”

“…Apoptotic death of some HC is followed by compensatory hypertrophy of Deiters' supporting cells (Fig. 3, e) with the formation of a permanent "epithelial cicatrix" [11], due to which the intact surface of the reticular plate is retained and further structural and functional disorders of acoustic perception at the adjacent OC sites with intact HC are prevented. b a c e d Fig.…”

Non-autonomous Cellular Responses to Ototoxic Drug-Induced Stress and Death

“…While many cell types in the inner ear internalize aminoglycosides, the HCs are particularly vulnerable to aminoglycoside-induced death. Aminoglycoside-induced HC death has been described as both apoptotic and necrotic (Nakagawa et al, 1998 ; Lenoir et al, 1999 ; Matsui et al, 2002 , 2003 ; Cunningham et al, 2004 ; Jiang et al, 2005 ). The molecular and cellular mechanisms that result in HC death are not fully understood, but there are a number of signaling molecules that are associated with aminoglycoside ototoxicity.…”

From Cochlear Cell Death Pathways To New Pharmacological Therapies

“…In the inner ear, moderate doses of ototoxins such as aminoglycosides or cisplatin have been shown to induce auditory sensory cell apoptosis in vitro [7][8][9] and in vivo [10][11][12]. Several recent publications studying the biological effects of sound and impulse sound trauma revealed that apoptosis is the predominant mode of hair cell death following such sound trauma [13][14][15].…”