Morphological consequences of acoustic trauma on cochlear hair cells and the auditory nerve.

AIMS: Hearing loss is the most common form of sensory impairment in humans. Short impulses of a high intensity noise can trigger sudden hearing loss, which is generally irreversible and associated with structural tissue damage of the cochlea and auditory nerve. It is well established that myelination is essential for the rapid propagation of action potentials along axons, and that Schwann cells are responsible for myelin sheath production in the peripheral nervous system. In the cochlea, spiral ganglion neuron axons are myelinated by Schwann cells. This myelin contributes to axonal protection and allows for efficient action potential transmission along the auditory nerve. For this reason, here we studie the morphological changes on cochlear hair cells and myelin sheaths of the auditory nerve, directly linked to hearing impairment induced by acoustic trauma. MATERIAL AND METHODS: To study the auditory functions, auditory brainstem responses and distortion products were measured at baseline, 2 days, and 21 days after trauma in rats. Then, scanning and transmission electron microscopy techniques were performed to analyze cochleae and the auditory nerve at 21 days after trauma. RESULTS: We observed that acoustic trauma induced cochlear outer hair cell loss and fusion of inner hair cell stereocilia. We also observed an axonal loss and myelin sheath disorganization of the auditory nerve. CONCLUSIONS: These data confirm that a strong acoustic trauma induced histological changes in the cochlea and auditory nerve, leading to permanent hearing loss.

Aminoglycosides use in patients over 75 years old.

OBJECTIVE: to describe aminoglycoside use and nephrotoxicity in patients older than 75 years. DESIGN: retrospective multicenter study. SETTING: hospital department, rehabilitation, long-term care center. POPULATION: patients ≥75 years old treated by aminoglycosides. RESULTS: 184 patients, mean age: 84.4 years (range: 75-101). One hundred and twenty-seven patients received other nephrotoxic drug(s). Gentamicin (70%) and amikacin (30%) were used and the once-daily dosing was preferred (92%). Average treatment period was 2.75 (1-10) days for amikacin and 4.4 (1-30) for gentamicin with average dosage 13.5 and 3.5 mg/kg/day, respectively. The monitoring of maximal plasmatic concentration (Cmax) was done in 37 patients, 9 of them had probabilistic treatment. Only one had a Cmax fulfilling the objective of French recommendations (gentamicin >30 mg/l, amikacin >60 mg/l). When infection was documented, the objective of Cmax >10 × minimal inhibitory concentration of the strain was reached for 27%. Minimal plasmatic concentration was checked in 38% of cases, with adequate value (gentamicin <0.5 mg/l, amikacin <2.5 mg/l) for 37%. At the end of aminoglycoside course, 40 patients increased their serum creatinine >25% of the baseline value. In multivariate analysis, this was associated with treatment length ≥3 days and concomitant use of nephrotoxic drugs. CONCLUSION: aminoglycosides dosing used in elderly patients probably need therapeutic drug monitoring and dose adjustment. Aminoglycosides are used to treat severe infections. One of the most important side effects is nephrotoxicity in oldest patients. To minimise nephrotoxicity, short treatments are necessary and avoiding others nephrotoxic drugs could be relevant.

N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model.

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly population. SAMP8 mouse model presents accelerated senescence and has been identified as a model of gerontological research. SAMP8 displays a progressive age-related decline in brain function associated with a progressive hearing loss mimicking human aging memory deficits and ARHL. The molecular mechanisms associated with SAMP8 senescence process involve oxidative stress leading to chronic inflammation and apoptosis. Here, we studied the effect of N-acetylcysteine (NAC), an antioxidant, on SAMP8 hearing loss and memory to determine the potential interest of this model in the study of new antioxidant therapies. We observed a strong decrease of auditory brainstem response thresholds from 45 to 75 days of age and an increase of distortion product amplitudes from 60 to 75 days in NAC treated group compared to vehicle. Moreover, NAC treated group presented also an increase of memory performance at 60 and 105 days of age. These results confirm that NAC delays the senescence process by slowing the age-related hearing loss, protecting the cochlear hair cells and improving memory, suggesting that antioxidants could be a pharmacological target for age-related hearing and memory loss.