The objectives of this proposal are to determine the features of cochlear blood flow (CBF) changes in response to both moderate acoustic stimulation and acoustic overstimulation. The experiments are designed to first, measure CBF changes in response to systematic tonotopic acoustic stimulation. Second, to measure alterations in vascular parameters in response to acoustic overstimulation, and to interfere with these alterations via peptidergic and hemodynamic manipulations. The methods implemented will be sound stimulation and intravital microscopy (IVM) measurement of blood flow changes.
The specific aims are: 1) to measure red blood cell velocity (Vrbc) and vessel diameter (Vd) changes in cochlear lateral wall vessels in response to moderate intensity tonotopic acoustic stimulation; 2) to determine the response of lateral wall vessels to acoustic overstimulation; 3) to determine the role of peptidergic- mediated blood flow regulation during acoustic overstimulation, and; 4) to determine the influence of hemorheologic changes on acoustic overstimulation-induced microvascular pathology. At the basic level, these experiments will determine a possible microvascular compensation in the cochlea in response to moderate intensity acoustic stimulation. This determination will provide an understanding of discrete and localized cochlear blood flow regulation in response to increased metabolic demand. Clinically, the examination of the influence of acoustic overstimulation on cochlear microcirculation will provide insight into the possibility that vascular dysfunctions contribute to noise-induced hearing loss (NIHL). The identification these vascular pathologies will enhance the development of treatment strategies not only for NIHL,but for other otopathologies suspected to be of vascular etiology.
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