Auditory efferent feedback system deficits precede age-related hearing loss: contralateral suppression of otoacoustic emissions in mice.

The C57BL/6J mouse has been a useful model of presbycusis, as it displays an accelerated age-related peripheral hearing loss. The medial olivocochlear efferent feedback (MOC) system plays a role in suppressing cochlear outer hair cell (OHC) responses, particularly for background noise. Neurons of the MOC system are located in the superior olivary complex, particularly in the dorsomedial periolivary nucleus (DMPO) and in the ventral nucleus of the trapezoid body (VNTB). We previously discovered that the function of the MOC system declines with age prior to OHC degeneration, as measured by contralateral suppression (CS) of distortion product otoacoustic emissions (DPOAEs) in humans and CBA mice. The present study aimed to determine the time course of age changes in MOC function in C57s. DPOAE amplitudes and CS of DPOAEs were collected for C57s from 6 to 40 weeks of age. MOC responses were observed at 6 weeks but were gone at middle (15-30 kHz) and high (30-45 kHz) frequencies by 8 weeks. Quantitative stereological analyses of Nissl sections revealed smaller neurons in the DMPO and VNTB of young adult C57s compared with CBAs. These findings suggest that reduced neuron size may underlie part of the noteworthy rapid decline of the C57 efferent system. In conclusion, the C57 mouse has MOC function at 6 weeks, but it declines quickly, preceding the progression of peripheral age-related sensitivity deficits and hearing loss in this mouse strain.

Contralateral suppression of distortion-product otoacoustic emissions declines with age: a comparison of findings in CBA mice with human listeners.

OBJECTIVES/HYPOTHESIS: The auditory efferent system plays presumed roles in enhancing signals in noise, maintaining the cochlea for optimal acoustic signal processing, and may have a protective role in preserving auditory function in the face of ototoxic events. The objective of the study was to measure age-related changes of the medial olivocochlear efferent system in mice by comparing distortion-product otoacoustic emissions generated with and without contralateral white noise stimulation. Consistent with prior work, distortion-product otoacoustic emissions were typically reduced in magnitude when white noise was presented to the contralateral ear. This contralateral suppression is attributed to activation of the medial olivocochlear efferent system, which has an inhibitory effect on the cochlear hair cell system. By studying contralateral suppression on cochlear output in subjects of different ages, it is possible to describe aging effects on the medial olivocochlear system. STUDY DESIGN: CBA mice were divided into three age groups: young adult, middle-aged, and old-aged animals (21, 13, and 22 animals per group, respectively), and auditory brainstem responses were obtained before distortion-product otoacoustic emission testing to assess overall hearing abilities. METHODS: 2f1-f2 distortion-product otoacoustic emission recordings were obtained from individual subjects (anesthetized with ketamine/xylazine) in each age group under two conditions: 1) in quiet and 2) in the presence of a contralaterally applied wideband noise. RESULTS: Principal findings were that distortion-product otoacoustic emission levels decreased with age for mice in a way similar to humans, when correcting for the absolute difference in life spans. In addition, contralateral suppression declined in middle-aged and old-aged groups relative to the young adults for mice in a manner similar to humans. The contralateral suppression decline at low frequencies preceded that of the decline in distortion-product otoacoustic emissions with age. CONCLUSION: Functional decline of the medial olivocochlear efferent system with age precedes outer hair cell degeneration. Loss of medial olivocochlear suppressive function may play a role in the development of presbycusis in both clinical cases and animal models.

Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome.

Although survival rates for acute respiratory distress syndrome have increased, there is only limited information regarding the quality of life and the relationship between quality of life and pulmonary function after survival. We prospectively measured pulmonary function, emotional function, and health-related quality of life in a cohort of acute respiratory distress syndrome survivors recruited from patients who were enrolled in a randomized clinical trial of high versus low tidal volume mechanical ventilation at 1 year after their recovery. No significant differences were found between the patients treated with high and low tidal volumes on any pulmonary function measure. Approximately 80% of the patients in both groups demonstrated reduced diffusing capacity; 20% had airflow obstruction, and 20% had chest restriction. Scores on measures of depression and anxiety were within the normal ranges, suggesting that they did not have significant affective symptoms. However, both groups reported decreased health-related quality of life in physical functioning, physical ability to maintain their roles (role-physical), bodily pain, general health, and vitality (energy) on the Medical Outcome Study Short Form Health Survey with similar physical limitations reported on the Sickness Impact Profile questionnaire. The pulmonary function abnormalities correlated with decreased health-related quality of life for domains reflecting physical function. Acute respiratory distress syndrome survivors treated with high and low tidal volumes have abnormal pulmonary function that was related to decreased health-related quality of life 1 year after hospital discharge.