Cellular Mechanisms of Noise-Induced Temporary Deafness

Mulroy, Michael

Abstract

This is a Shannon award providing partial support for the research projects that fall short of the assigned Institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. DESCRIPTION: Recent studies of tissues which are normally subjected to mechanical stress such as muscle and vascular endothelium suggest that excessive mechanical stress can cause lesions in the plasmalemma of those cells. Some of the lesions are lethal to cells, but some are transitory with the cells being able to patch the lesion and recover. There is also evidence that the damaged cells release through the lesions a diffusible substance, a """"""""wound hormone"""""""" that promotes recovery of those cells. Auditory hair cells are subjected to excessive mechanical stress when acoustically overstimulated. This raises the interesting possibility that the same mechanisms may apply to the inner ear. The experiments proposed are designed to test the hypothesis that one of the cellular mechanisms responsible for noise-induced temporary deafness is that the noise exposure causes temporary microlesions in plasma membranes of auditory hair cells. A labeled molecule, which does not normally enter cells, will be introduced in vivo into the extracellular fluid around hair cells. If the marker enters the cells and diffuses throughout the cytoplasm, this will be interpreted as a sign of temporary membrane wounding. An in vitro preparation of the auditory organ will be used to selectively perfuse either the stereociliary or basolateral membranes of hair cells to determine the sites of the lesions. Three neurotrophic factors, basic fibroblast growth factor, acidic fibroblast growth factor and ciliary neurotropic factor, are thought to be released from wounded cells by diffusing out from the cytoplasm through lesions in the membrane to stimulate recovery of that tissue. Antibodies will be used to test for the presence of these neurotropic factors in the cytoplasm of hair cells. These neurotropic factors will be injected into the cochlea to determine if they improve the rate of recovery from noise-induced temporary deafness using neurophysiological criterion of recovery. The existence of a substance, which promotes survival and recovery of mechanically damaged cells would suggest the exciting possibility that such a substance might be useful as a therapeutic agent to promote recovery from acoustic trauma.