Neuroimmunological Activation of Afferent Auditory Neural Circuit in LPS-Induced Otitis Media / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: The goal of this study was to identify the central modulation of the auditory pathway by peripheral inflammation and loud sound exposure, which is associated with proinflammatory cytokines. MATERIALS AND METHOD: Eight male adult Sprague-Dawley rats were exposed to 125-8,000 Hz, 90 dB white noise for three hours. Immediately, 6 hours, 24 hours, and 3 days after the sound stimuli, 2 rats were sacrificed respectively. For the inflammatory stimuli, 10 rats were inoculated with LPS (100 microgram/50 microliter) through ipsilateral tympanic membrane. In 3 hours, 6 hours, 24 hours, 3 days and 7 days, 2 rats were sacrificed respectively. The brains of rats were prepared including the cochlear nucleus and inferior colliculus. The brains were stained for c-fos (proto-oncogene proteins) and IL-1beta. Two normal control rats were sacrificed without treatment. RESULTS: In the noise exposure group, c-fos and IL-1beta were expressed along the previously known auditory neural pathway and some non-hearing-related nuclei. In the LPS injection group, the c-fos and inflammatory cytokine IL-1beta were mainly expressed along the ascending afferent auditory pathway such as cochlear nucleus, trapezoid body, lateral lemniscus, inferior colliculus. IL-1beta expression was also found in the nuclei of non auditory pathway such as locus coeruleus, lateral parabrachial nucleus, and vestibular nucleus. CONCLUSION: These results show that inflammatory reactions of peripheral middle ear cavity and loud sound exposure may induce expression of proinflammatory cytokines along the afferent auditory circuit and the functional auditory pathway. It might be suggested that peripheral changes by inflammation or loud sound could induce functional and physiologic alterations in the auditory system via neuroimmunomodulation.