Fibrovascular coupling in the cochlea and pericyte recruitment after noise

噪声后耳蜗中的纤维血管耦合和周细胞募集

基本信息

批准号：
8664362
负责人：
Xiaorui Shi
金额：
$ 37.27万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8664362
关键词：
Action Potentials Affect Animals Astrocytes Attenuated Blood Blood Flow Velocity Blood Vessels Blood capillaries Blood flow Bone Marrow Cell Transplantation Brain Bromodeoxyuridine Calcium Caliber Clinical Clinical Management Clinical Treatment Cochlea Computer software Confocal Microscopy Coupled Coupling Custom Development Dinoprostone Disease Electrophysiology (science)Enzyme-Linked Immunosorbent Assay Extravasation Fluid Balance Foundations Functional disorder Goals Hair Cells Hearing Hearing problem Image Immune Immunoglobulin G In Vitro Ions Knockout Mice Knowledge Label Laboratories Labyrinth Ligaments Link Measures Medical Metabolic Methods Microcirculation Molecular Neuroglia Neurons Nitric Oxide Nitric Oxide Pathway Noise Noise-Induced Hearing Loss Pathology Pathway interactions Pericytes Permeability Physiology Play Population Presbycusis Production Prostaglandin-Endoperoxide Synthase Proto-Oncogene Proteins c-sis Recovery Recycling Regional Blood Flow Regulation Research Retina Reverse Transcriptase Polymerase Chain Reaction Role Sensorineural Hearing Loss Serum Proteins Signal Pathway Signal Transduction Smooth Muscle Staining method Stains Stem cells Stria Vascularis Testing Tinnitus Transplantation Trauma Up-Regulation Vascular Diseases Vascular Endothelial Growth Factors Vascular Permeabilities Vascular blood supply Western Blotting base capillary density disorder prevention foot hearing impairment in vivo inner ear diseases intravital fluorescence microscopy meetings photolysis repaired round window sound

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：耳蜗微循环对于正常听力至关重要，耳蜗血流量减少和血迷路屏障（BLB）破坏与许多听力障碍有关。开发血管相关性听力损失的新疗法需要更好地了解耳蜗血流 (CBF) 的控制和 BLB 的修复。特别是，我们需要了解微循环水平的局部细胞控制机制，以及血管恢复中涉及的细胞修复机制。我们的早期研究结果表明，周细胞通过收缩活动控制局部 CBF 并在创伤引起的 BLB 损伤后重塑脉管系统。然而，控制周细胞收缩和适应性活动的信号通路尚未确定。在大脑和视网膜中，由神经元、星形胶质细胞、周细胞和平滑肌组成的“神经血管单元”（NVU）可直接、快速地调节局部血流以满足代谢需求。耳蜗纤维细胞类似于星形胶质细胞和神经胶质细胞，在从毛细胞回收 K+ 中发挥作用，被发现在形态上与螺旋韧带前毛细血管上的周细胞相连。研究结果表明，可能存在一种类似于 NVU 的机制来调节耳蜗微循环中的血流。因此，该提案包括四个进一步研究的目标：1）纤维细胞-周细胞耦合在周细胞调节和CBF控制中的作用； 2）纤维细胞-周细胞单位的信号传导机制； 3）纤维细胞-周细胞耦合在声音活动和CBF之间的桥梁中的功能作用； 4) 健全产生的 BLB 中周细胞的募集。这项研究通过提供有关纤维细胞和周细胞功能的基础知识，将为更好地临床治疗内耳疾病、预防周细胞相关的血管损伤以及开发有效的听力损失临床治疗方法奠定基础。