The Middle Ear Muscle Reflex in Rat: Developing a Biomarker of Auditory Nerve Degeneration.

OBJECTIVES: The long-term goal of this research is to determine whether the middle ear muscle reflex can be used to predict the number of healthy auditory nerve fibers in hearing-impaired ears. In this study, we develop a high-impedance source and an animal model of the middle ear muscle reflex and explore the influence of signal frequency and level on parameters of the reflex to determine an optimal signal to examine auditory nerve fiber survival. DESIGN: A high-impedance source was developed using a hearing aid receiver attached to a 0.06 diameter 10.5-cm length tube. The impedance probe consisted of a microphone probe placed near the tip of a tube coupled to a sound source. The probe was calibrated by inserting it into a syringe of known volumes and impedances. The reflex in the anesthetized rat was measured with elicitor stimuli ranging from 3 to 16 kHz presented at levels ranging from 35 to 100 dB SPL to one ear while the reflex was measured in the opposite ear containing the probe and probe stimulus. RESULTS: The amplitude of the reflex increased with elicitor level and was largest at 3 kHz. The lowest threshold was approximately 54 dB SPL for the 3-kHz stimulus. The rate of decay of the reflex was greatest at 16 kHz followed by 10 and 3 kHz. The rate of decay did not change significantly with elicitor signal level for 3 and 16 kHz, but decreased as the level of the 10-kHz elicitor increased. A negative feedback model accounts for the reflex decay by having the strength of feedback dependent on auditory nerve input. The rise time of the reflex varied with frequency and changed with level for the 10- and 16-kHz signals but not significantly for the 3-kHz signal. The latency of the reflex increased with a decrease in elicitor level, and the change in latency with level was largest for the 10-kHz stimulus. CONCLUSIONS: Because the amplitude of the reflex in rat was largest with an elicitor signal at 3 kHz, had the lowest threshold, and yielded the least amount of decay, this may be the ideal frequency to estimate auditory nerve survival in hearing-impaired ears.

Interleukin-23-mediated inflammation in Pseudomonas aeruginosa pulmonary infection.

Pseudomonas aeruginosa is an opportunistic pathogen that is capable of causing acute and chronic pulmonary infection in the immunocompromised host. In the case of cystic fibrosis (CF), chronic P. aeruginosa infection causes increased mortality by promoting overly exuberant airway inflammation and cumulative lung damage. Identifying the key regulators of this inflammation may lead to the development of new therapies that improve P. aeruginosa-related mortality. We report here that interleukin-23 (IL-23), the cytokine most clearly tied to IL-17-mediated inflammation, also promotes IL-17-independent inflammation during P. aeruginosa pulmonary infection. During the early innate immune response, prior to IL-17 induction, IL-23 acts synergistically with IL-1ß to promote early neutrophil (polymorphonuclear leukocyte [PMN]) recruitment. However, at later time points, IL-23 also promoted IL-17 production by lung γδ T cells, which was greatly augmented in the presence of IL-1ß. These studies show that IL-23 controls two independent phases of neutrophil recruitment in response to P. aeruginosa infection: early PMN emigration that is IL-17 independent and later PMN emigration regulated by IL-17.