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Macrophage Response to Otic Pathology

巨噬细胞对耳部病理学的反应

基本信息

批准号：
10667639
负责人：
Mark Warchol
金额：
$ 43.34万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10667639
关键词：
Acoustic Nerve Acute Affect Afferent Neurons Brain Cause of Death Cell Death Cell Survival Cells Clustered Regularly Interspaced Short Palindromic Repeats Cochlea Cochlear Implants Cochlear implant procedure Cytomegalovirus Cytomegalovirus Infections Data Development Dizziness Eating Effector Cell Epithelium Equilibrium Excision Exposure to Family Hair Cells Head Movements Hearing Homeostasis Human Infection Inflammation Inflammatory Inflammatory Response Injury Innate Immune System Inner Ear Infection Inner Hair Cells Knowledge Labyrinth Lesion Macrophage Mechanics Mediating Membrane Modeling Morphology Motion Mus Natural Immunity Natural regeneration Neomycin Organ Pathology Peripheral Phagocytes Phagocytosis Phagocytosis Inhibition Phosphatidylserines Phosphotransferases Pilot Projects Play Population Process Recovery of Function Role Sensory Sensory Hair Signal Pathway Signal Transduction Site Stereotyping Supporting Cell Surface System Testing Tissues Utricle structure Vertebrates Vertigo Vestibular Hair Cells Vestibular Nerve Vestibular loss Virus Diseases Zebrafish cell injury cell type clinically relevant equilibration disorder experience experimental study hair cell regeneration implantation injured injury recovery lateral line macula member method development migration mouse model neonatal mice neuromast noise exposure normal aging ototoxicity ototoxin prenatal prevent receptor recruit repaired response sound tissue repair transmission process vibration

项目摘要

The senses of hearing and balance are mediated by the cochlea and vestibular organs of the inner ear. In these organs, mechanical motion (generated either by sound vibrations or by head movements) is detected by sensory hair cells and transmitted to the brain by the auditory and vestibular nerves. Hair cells are essential for sensory function, but can be injured by noise exposure, ototoxicity or infections, and are also lost as a consequence of normal aging. After injury, the timely removal of cellular debris from the sensory epithelium helps promote repair and homeostasis. This process is mediated by two distinct cell types: (1) Supporting cells, which can engulf cellular debris and – in nonmammalian vertebrates – generate replacement hair cells, and (2) Macrophages, which are effector cells of the innate immune system that also recognize and engulf dying cells. Supporting cells are present in all hair cell-containing epithelia. The tissues of the inner ear also contain resident populations of macrophages, and macrophage-mediated inflammation occurs after most types of otic injury. When responding to hair cell injury, it is critical that both supporting cells and macrophages correctly distinguish between healthy and dying cells, and then target and remove only those cells that are irreversibly damaged. A key objective of this project is to understand how this process occurs. One set of experiments will examine a signaling pathway known to be essential for evoking phagocytic responses in macrophages and other cell types, but has not been previously studied in the inner ear. In addition, we will determine whether inhibiting phagocytosis after acute injury may permit some damaged hair cells to survive, and whether the engulfment of injured hair cells is an important trigger for sensory regeneration. Studies will employ both mammalian and zebrafish models, in order to best utilize the unique advantages of both systems. A second set of experiments will enhance our very limited knowledge of the role of inflammation in the vestibular organs. Projects will focus on two clinically relevant situations. First, it is known that prenatal infection with cytomegalovirus (CMV) can cause developmental deficits in both hearing and balance, but the underlying mechanisms are completely unknown. Using a validated mouse model, we have shown that CMV infection leads to a massive inflammatory response in the vestibular maculae, which is accompanied by phagocytosis of sensory cells. We will determine whether this inflammation is the cause of CMV-induced pathology and also whether macrophages transport CMV into the vestibular periphery. Additional studies will characterize vestibular injury and inflammation in a mouse model of cochlear implantation. Completion of the studies will greatly enhance current knowledge of the cellular signals that regulate inflammation in the inner ear. Such knowledge will permit development of methods for modulating such inflammation, so as to reduce pathology and enhance functional recovery after injury.

听觉和平衡感是由内耳的耳蜗和前庭器官调节的。在

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Macrophage recruitment and epithelial repair following hair cell injury in the mouse utricle.

DOI：
10.3389/fncel.2015.00150
发表时间：
2015
期刊：
Frontiers in cellular neuroscience
影响因子：
5.3
作者：
Kaur T;Hirose K;Rubel EW;Warchol ME
通讯作者：
Warchol ME

Characterization of supporting cell phenotype in the avian inner ear: implications for sensory regeneration.

鸟类内耳支持细胞表型的表征：对感觉再生的影响。

DOI：
10.1016/j.heares.2006.08.014
发表时间：
2007
期刊：
Hearing research
影响因子：
2.8
作者：
Warchol,MarkE
通讯作者：
Warchol,MarkE

Macrophage Depletion Protects Against Cisplatin-Induced Ototoxicity and Nephrotoxicity.

巨噬细胞耗竭可防止顺铂引起的耳毒性和肾毒性。

DOI：
10.1101/2023.11.16.567274
发表时间：
2023
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Sung,CathyYeaWon;Hayase,Naoki;Yuen,PeterST;Lee,John;Fernandez,Katharine;Hu,Xuzhen;Cheng,Hui;Star,RobertA;Warchol,MarkE;Cunningham,LisaL
通讯作者：
Cunningham,LisaL

Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function.