The cochlear microcirculation is essential for normal hearing. A reduction of cochlear blood flow is involved in a number of hearing disorders. Pericytes, surrounding blood microvessels, play important roles for many organs in the regulation of microvessel blood flow by responding to a wide variety of vasoactive agonists. They also affect the microvessel wall integrity by synthesizing and secreting structural constituents of the basement membrane and extracellular matrix. Pericyte physiology and their density along the microvessels exhibit tissue-related and vessel-related specificity. Their distribution and locations are tightly coupled to functional and metabolic needs. We have previously found a high density of pericytes on the capillaries of the cochlear lateral wall: in the stria vascularis and spiral ligament. We hypothesize that they regulate cochlear microcirculation through their contraction. Therefore, the goals of this project are to determine the contractile activity of lateral wall pericytes, their physiology and their involvement in the loud sound induced inner ear blood flow alteration.
In Aim 1, we will induce and measure pericyte contractility in vitro;
In Aim 2, we will induce and measure pericyte contractility in vivo. A long-term goal is to understand cochlear signaling pathways of pericyte related-regulatory mechanisms in cochlear blood flow and their involvement in cochlear fluid hemostasis. The volume of cochlear blood flow is extremely small (on the order of 1/1 000 000 of total cardiac output), yet critically important for normal hearing. Dysfunctions in the cochlear blood supply can cause serious hearing disorders including sudden sensorineural hearing loss, presbyacusis, noise-induced hearing loss, tinnitus, and certain vestibulopathies. In clinical practice vasoactive substances have been have not been very effective because we do not have an understanding of the circulation. In this research project, we will investigate the pericyte (smooth muscle-like cells and also a progenitor cell to generate macrophages and phagocytes, fibroblasts, and smooth muscle cells) related regulatory mechanisms of cochlear microcirculation and gain a deeper understanding of the mechanisms that control of blood flow in order to develop effective clinical medical therapies for inner ear disease. ? ? ? ?
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