Cochlear fluid disturbances are a major facto in a number of pathologies affecting the inner ear, such as Meniere's disease. The goal of our studies is to provide a scientific basis for the diagnosis and treatment of endolymph volume disturbances. A direct approach is used, based on sensitive techniques, which measure endolymph volume and flow in vivo. Using these measures, we will establish a number of methods, which influence endolymph volume, including infrasonic, and low frequency tones and pressure pulses delivered to the cochlear fluids or ear canal. Ossicular movements induced by some of these stimuli are comparable to those induced by middle middle muscle contractions which have been shown to generate endolymph movements. Mechanisms underlying volume disturbance and those contributing to volume recovery will be investigated. During volume manipulations, indirect methods for quatifying endolymph volume changes will be correlated with direct measurements of endolymphatic cross-sectional area. These studies will lead to improved diagnostic tests for endolymphatic hydrops. A second project will examine physiologic changes occurring in the endolymphatic sac during manipulations of endolymph volume in the cochlea. The magnitude and time course of electrolyte changes in the sac will be measured during disturbances. The time course and spatial distribution of induced anatomical changes of the sac will be documented and quantified using 3-D magnetic resonance microscopy, light and electron microscopy. The functional role played by the endolymphatic sac will be incorporated into quantitative mathematical models of solute dispersion in the inner ear. These studies will identify possible mechanisms by which the sac regulates endolymph volume and will lead to more sophisticated methods for treating endolymph volume disturbances. They will also direct future studies to the tissues and processes underlying specific aspects of volume regulation. The project as a whole will establish the fundamental physiological processes contributing to endolymph volume regulation and will have relevance to the clinical diagnosis and treatment of cochlear fluid disorders.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Platt, Christopher
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Washington University
Schools of Medicine
Saint Louis
United States
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Salt, Alec N; Plontke, Stefan K (2018) Pharmacokinetic principles in the inner ear: Influence of drug properties on intratympanic applications. Hear Res 368:28-40
Li, Wei; Hartsock, Jared J; Dai, Chunfu et al. (2018) Permeation Enhancers for Intratympanically-applied Drugs Studied Using Fluorescent Dexamethasone as a Marker. Otol Neurotol 39:639-647
Salt, Alec N; Hirose, Keiko (2018) Communication pathways to and from the inner ear and their contributions to drug delivery. Hear Res 362:25-37
Liebau, Arne; Pogorzelski, Olivia; Salt, Alec N et al. (2017) Hearing Changes After Intratympanically Applied Steroids for Primary Therapy of Sudden Hearing Loss: A Meta-analysis Using Mathematical Simulations of Drug Delivery Protocols. Otol Neurotol 38:19-30
Lichtenhan, J T; Hirose, K; Buchman, C A et al. (2017) Direct administration of 2-Hydroxypropyl-Beta-Cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements. PLoS One 12:e0175236
Plontke, Stefan K; Hartsock, Jared J; Gill, Ruth M et al. (2016) Intracochlear Drug Injections through the Round Window Membrane: Measures to Improve Drug Retention. Audiol Neurootol 21:72-9
Salt, Alec N; Plontke, Stefan K (2016) Drug Diffusion to the Apex of the Human Cochlea? A Comment on ""Kang WS, Nguyen K, McKenna CE, Sewell WF, McKenna MJ, Jung DH. Intracochlear Drug Delivery Through the Oval Window in Fresh Cadaveric Human Temporal Bones"". Otol Neurotol 37:1462-3
Lichtenhan, J T; Hartsock, J; Dornhoffer, J R et al. (2016) Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral. J Neurosci Methods 273:201-209
Salt, A N; Hartsock, J J; Gill, R M et al. (2016) Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig. Hear Res 342:101-111
Ellis, Erica M; Borovsky, Arielle; Elman, Jeffrey L et al. (2015) Novel word learning: An eye-tracking study. Are 18-month-old late talkers really different from their typical peers? J Commun Disord 58:143-57

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