Basic study on the progression and protective mechanisms of cochlear disorders

Abstract

　　In cochlear disorders, various mechanisms have been identified to promote and inhibit the progression of damage. Herein, we summarize the findings from animal experiments conducted to study cochlear ischemia-reperfusion injury and drug-induced hearing loss. The involvement of reactive oxygen species and glutamic acid in the progression of damage has been confirmed, and neuroexcitotoxicity due to glutamic acid has been observed in cochlear afferent neurons. Damage caused by reactive oxygen species is primarily observed in the hair cells, where reactive oxygen species activate various kinase pathways, leading to caspase activation and apoptosis of the hair cells. Additionally, reactive oxygen species are also known to cause ribbon synapse damage in the inner hair cells, contributing to hidden hearing loss.

　　Lipid mediators have been found to be involved in suppressing the progression of cochlear disorders. Ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) are generated from sphingomyelin and function as endogenous cell-protective factors. The protective effect of the female hormone estrogen on the cochlea has also been recognized. Thus, in cochlear disorders, both detrimental and protective factors are known to operate within the cochlea, the balance between the two determining the fate of the hair cells.