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.
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.
|Hou, Zhiqiang; Wang, Xiaohan; Cai, Jing et al. (2018) Platelet-Derived Growth Factor Subunit B Signaling Promotes Pericyte Migration in Response to Loud Sound in the Cochlear Stria Vascularis. J Assoc Res Otolaryngol 19:363-379|
|Zhang, Jinhui; Chen, Songlin; Cai, Jing et al. (2017) Culture media-based selection of endothelial cells, pericytes, and perivascular-resident macrophage-like melanocytes from the young mouse vestibular system. Hear Res 345:10-22|
|Ben Said, Mariem; Grati, M'hamed; Ishimoto, Takahiro et al. (2016) A mutation in SLC22A4 encoding an organic cation transporter expressed in the cochlea strial endothelium causes human recessive non-syndromic hearing loss DFNB60. Hum Genet 135:513-24|
|Shi, Xiaorui (2016) Pathophysiology of the cochlear intrastrial fluid-blood barrier (review). Hear Res 338:52-63|
|Yang, Yuqin; Chen, Fangyi; Karasawa, Takatoshi et al. (2015) Diverse Kir expression contributes to distinct bimodal distribution of resting potentials and vasotone responses of arterioles. PLoS One 10:e0125266|
|Zhang, Jinhui; Chen, Songlin; Hou, Zhiqiang et al. (2015) Lipopolysaccharide-induced middle ear inflammation disrupts the cochlear intra-strial fluid-blood barrier through down-regulation of tight junction proteins. PLoS One 10:e0122572|
|Neng, Lingling; Zhang, Jinhui; Yang, Ju et al. (2015) Structural changes in thestrial blood-labyrinth barrier of aged C57BL/6 mice. Cell Tissue Res 361:685-96|
|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|
|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|
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