Age-related hearing loss (AHL), also known as presbycusis, is a universal feature of mammalian aging and is characterized by a decline of auditory function, such as increased hearing thresholds and poor frequency resolution. The primary pathology of AHL includes the hair cells, stria vascularis, and afferent spiral ganglion neurons as well as the central auditory pathways. A growing body of evidence in animal studies has suggested that cumulative effect of oxidative stress could induce damage to macromolecules such as mitochondrial DNA (mtDNA) and that the resulting accumulation of mtDNA mutations/deletions and decline of mitochondrial function play an important role in inducing apoptosis of the cochlear cells, thereby the development of AHL. Epidemiological studies have demonstrated four categories of risk factors of AHL in humans: cochlear aging, environment such as noise exposure, genetic predisposition, and health co-morbidities such as cigarette smoking and atherosclerosis. Genetic investigation has identified several putative associating genes, including those related to antioxidant defense and atherosclerosis. Exposure to noise is known to induce excess generation of reactive oxygen species (ROS) in the cochlea, and cumulative oxidative stress can be enhanced by relatively hypoxic situations resulting from the impaired homeostasis of cochlear blood supply due to atherosclerosis, which could be accelerated by genetic and co-morbidity factors. Antioxidant defense system may also be influenced by genetic backgrounds. These may explain the large variations of the onset and extent of AHL among elderly subjects.

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The administration of methimazole is known to induce cell death in rat olfactory receptor neurons (ORNs). We investigated whether this injury occurs via apoptosis or through necrosis and whether it involves the extrinsic or intrinsic pathway. Rats were intraperitoneally injected with vehicle (control) or 300 mg/kg methimazole. The experimental animals were also administered vehicle or a caspase-3 or caspase-9 inhibitor 30 min earlier. The administration of methimazole induced cell death predominantly in the mature ORNs and partially reduced olfactory sensitivity in the rats; the injured cells were TUNEL-positive and showed a nuclear staining pattern. This insult induced cytochrome c release from the mitochondria and a significant increase in the immunoreactivity of activated caspase-3 and caspase-9 as well as that of cleaved poly-ADP-ribose-polymerase; in addition, it caused a significant increase in the fluorogenic activity of caspase-3 and caspase-9. However, it did not affect the immunoreactivity of activated caspase-8 or the fluorogenic activity of caspase-8. Pretreatment with a caspase-3 or caspase-9 inhibitor nearly completely prevented the morphologic, biochemical, and functional changes induced by methimazole. These findings suggest strongly that methimazole-induced cell death in rat ORNs is predominantly apoptosis; moreover, the majority of this apoptotic cell death is triggered through mitochondrial cytochrome c-mediated caspase-3 activation pathway, and both caspase-3 and caspase-9 inhibitors can prevent methimazole-induced cell death in the ORNs.

The RWN visibility and the preoperative HRCT findings showed a high correlation. Drawing the prediction line is a simple and useful way for preoperatively predicting the RWN visibility in cochlear implant surgery.

1) The nerve of origin of tumors cannot be predicted based on caloric response and VEMP. 2) In the intermediate and medial types, caloric response and the VEMP amplitude are significantly diminished in association with an increase in tumor size. 3) Prolonged VEMP latencies seem to be not only caused by tumor compression to the brainstem or vestibular spinal tract but also by tumor compression isolated to the inferior vestibular nerve.