Cochlear microcirculation is essential for normal hearing, with reduction of cochlear blood flow and disruption of blood-labyrinth barrier (BLB) involved in a number of hearing disorders. Development of new treatments for vascular-related hearing loss requires a better understanding of control over cochlear blood flow (CBF) and repair of the BLB. In particular, we need to understand the local cellular control mechanisms at the level of the microcirculation, as well as the cellular repair mechanisms involved in vascular recovery. Our early findings suggest that pericytes play roles in controlling regional CBF through contractile activity and remodeling the vasculature after trauma-induced BLB damage. The signaling pathways, however, that control the contractile and adaptive activities of pericytes have not been identified. In the brain and retina, "neuro-vascular units" (NVUs), consisting of neurons, astrocytes, pericytes, and smooth muscle, provide direct and swift modulation of local blood flow to match metabolic demand. Cochlear fibrocytes, which resemble astrocytes and glial cells and play a role in recycling K+ from hair cells, are found to be morphologically connected to pericytes on the spiral ligament pre-capillaries. The findings suggest there may be a mechanism analogous to the NVU for regulation of blood flow in the cochlear microcirculation. This proposal, therefore, comprises four Aims to further investigate: 1) the role of fibrocyte-pericyte coupling in the regulation of pericytes and control of CBF;2) the signaling mechanism of the fibrocyte-pericyte unit;3) the functional role of fibrocyte-pericyte coupling in bridging between sound activity and CBF;and 4) pericyte recruitment in sound-produced BLB. This study, by providing fundamental knowledge on fibrocyte and pericyte function, will lay the foundation for better clinical management of inner ear disease, prevention of pericyte-related vascular damage, and development of effective clinical treatments for hearing loss.

Public Health Relevance

A wide array of hearing disorders, including sudden sensorineural hearing loss, presbycusis, noise-induced hearing loss, tinnitus, auto-immune hearing loss, and vestibular disorders, involve dysfunction of the blood supply to the cochlea and disruption of the blood-labyrinth barrier (BLB) in the inner ear. It follows that development of new treatments for vascular disorder-related hearing loss will require a better understanding of cochlear blood flow and BLB physiology and pathology. The findings from this study will provide the basis for development of effective medical therapies for inner ear disease.

National Institute of Health (NIH)
Research Project (R01)
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Auditory System Study Section (AUD)
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Cyr, Janet
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Oregon Health and Science University
Schools of Medicine
United States
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Wilson, Teresa; Omelchenko, Irina; Foster, Sarah et al. (2014) JAK2/STAT3 inhibition attenuates noise-induced hearing loss. PLoS One 9:e108276
Shi, Xiaorui; Zhang, Fei; Urdang, Zachary et al. (2014) Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow. Hear Res 313:38-46
Zhang, Fei; Dai, Min; Neng, Lingling et al. (2013) Perivascular macrophage-like melanocyte responsiveness to acoustic trauma--a salient feature of strial barrier associated hearing loss. FASEB J 27:3730-40
Neng, Lingling; Zhang, Wenjing; Hassan, Ahmed et al. (2013) Isolation and culture of endothelial cells, pericytes and perivascular resident macrophage-like melanocytes from the young mouse ear. Nat Protoc 8:709-20
Han, Wei-ju; Shi, Xiao-rui; Nuttall, Alfred (2013) Noise-induced nitrotyrosine increase and outer hair cell death in guinea pig cochlea. Chin Med J (Engl) 126:2923-7
Zhang, Fei; Zhang, Jinhui; Neng, Lingling et al. (2013) Characterization and inflammatory response of perivascular-resident macrophage-like melanocytes in the vestibular system. J Assoc Res Otolaryngol 14:635-43
Neng, Lingling; Zhang, Fei; Kachelmeier, Allan et al. (2013) Endothelial cell, pericyte, and perivascular resident macrophage-type melanocyte interactions regulate cochlear intrastrial fluid-blood barrier permeability. J Assoc Res Otolaryngol 14:175-85
Dai, Min; Shi, Xiaorui (2011) Fibro-vascular coupling in the control of cochlear blood flow. PLoS One 6:e20652
Dai, Min; Yang, Yue; Shi, Xiaorui (2011) Lactate dilates cochlear capillaries via type V fibrocyte-vessel coupling signaled by nNOS. Am J Physiol Heart Circ Physiol 301:H1248-54
Wu, T; Song, L; Shi, X et al. (2011) Effect of capsaicin on potassium conductance and electromotility of the guinea pig outer hair cell. Hear Res 272:117-24

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