Strial vascular pathology from acoustic trauma
声损伤引起的心房血管病理学
基本信息
- 批准号:9383753
- 负责人:
- 金额:$ 42.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:Acoustic TraumaAffectAfferent NeuronsAgingAnimalsAuditoryBasement membraneBiologicalBiological PreservationBloodBlood VesselsBlood capillariesBlood flowBrainBromodeoxyuridineCaliberCardiacCardiologyCell LineCellsClinicalCochleaCommunicationConfocal MicroscopyDevelopmentDiseaseEarEdemaElectron MicroscopyEmployee StrikesEndothelial CellsEnergy SupplyExposure toExtravasationFailureFoundationsFunctional disorderGene DeliveryGoalsGrowth FactorHair CellsHealthHearingHearing problemHeartHormonesHumanHypoxiaImmunophenotypingImpairmentIn VitroIndividualInfarctionInjuryKidney DiseasesLabelLabyrinthLateralLeadLifeLigandsLoudnessMaintenanceMediatingMembrane ProteinsMesenchymalMetabolicModelingMolecularMusMyocardial InfarctionMyofibroblastNatural regenerationNeonatalNeuronsNoiseNuclearOrganPDGFA genePathologicPathologyPericytesPhenotypePhysiologyPlatelet-Derived Growth Factor beta ReceptorPopulationProductionProliferatingPropertyProteinsProto-Oncogene Proteins c-sisRecoveryRegulationReporterResearchResidual stateResolutionRetinaRetinalRoleSensorySignal PathwaySignal TransductionSiteSocial isolationSourceStem cellsStressStria VascularisStrokeStructureSudden DeafnessSystemTestingTissuesTransforming Growth Factor betaTransforming Growth FactorsTransgenic MiceTransplantationTraumaVascular DiseasesVascular blood supplyWound Healingangiogenesisbaseblood perfusioncapillarydeafnessdensitydiabetic patientfibrogenesishearing impairmentimprovedinhibitor/antagonistinjuredmatrigelmigrationnetwork modelsneurotrophic factornovelnovel strategiespigment epithelium-derived factorplatelet-derived growth factor BBpreventprotein expressionreceptorrepairedrestorationsoundsuccesstherapeutic target
项目摘要
PROJECT SUMMARY
Energy supply to the ear is critical for hearing function since the ear is one of the highest energy consuming
organs. Insufficient energy can result from insufficient blood flow to the cochlea contributing to a wide range of
clinical hearing disorders such as loud sound-induced hearing loss, hearing loss related to ageing, and sudden
deafness, which can largely impact the quality of human life by causing individual communication problems
and social isolation. We believe that success in repair and regeneration of hearing function following loss of
sensory cells requires parallel restoration or maintenance of an efficient blood supply. The proposed research
is part of a longer range study on the role of pericytes in the physiology of the cochlea, but is specifically
focused on the pericyte pathology that occurs in loud sound-induced lateral wall microcirculatory dysfunction.
Pericytes are multipotent mesenchymal-like cells and are primarily located on microvessels. Normal function of
pericytes is vital for blood flow regulation, vascular integrity, angiogenesis and tissue fibrogenesis. Pericyte
pathology is profoundly associated with many organ diseases such as brain stroke, heart infarction, and retinal
failure. Therapeutic targeting of pericytes has been considered a novel treatment for many of those clinical
diseases. Cochlear pericytes are extremely vulnerable and sensitive to damage, but are critical for regulation
of cochlear blood flow and maintaining tightness of the blood-labyrinth barrier in the stria vascularis. More
specifically they are highly responsive to stress such as acoustic trauma. Upon exposure to loud sound,
cochlear pericytes undergo striking changes in their biological properties, but the molecular mechanisms that
underline those changes have not yet been studied. In this five year proposal, we will determine what
molecular signals lead to loud sound-induced pericyte migration away from the capillaries and their phenotype
changes. We will also determine whether transplantation of fresh pericytes such as neo-pericytes (derived from
neonatal mice) to noise-damaged cochlea can repair loud sound-damaged microvessels and restore vascular
function. The success of each aim will inevitably lead to the development of new protective and restorative
therapies for a normal blood flow to cochlea― the critical foundation of hearing preservation or/and restoration.
项目概要
耳朵的能量供应对于听力功能至关重要,因为耳朵是能量消耗最高的部位之一
器官。耳蜗血流不足可能导致能量不足,从而导致多种问题
临床听力障碍,例如大声引起的听力损失、与衰老相关的听力损失以及突发性听力损失
耳聋,会导致个人沟通问题,从而在很大程度上影响人类的生活质量
和社会隔离。我们相信,听力损失后听力功能的修复和再生的成功
感觉细胞需要同时恢复或维持有效的血液供应。拟议的研究
是关于周细胞在耳蜗生理学中的作用的长期研究的一部分,但具体是
专注于大声声音引起的侧壁微循环功能障碍中发生的周细胞病理学。
周细胞是多能间充质样细胞,主要位于微血管上。正常功能
周细胞对于血流调节、血管完整性、血管生成和组织纤维生成至关重要。周细胞
病理学与许多器官疾病密切相关,例如脑中风、心脏病和视网膜疾病
失败。针对周细胞的治疗靶向已被认为是许多临床治疗的一种新疗法。
疾病。耳蜗周细胞极其脆弱且对损伤敏感,但对于调节至关重要
耳蜗血流并维持血管纹中血迷路屏障的紧密性。更多的
具体来说,它们对声损伤等压力高度敏感。当暴露在大声的声音中时,
耳蜗周细胞的生物学特性经历了显着的变化,但其分子机制
强调这些变化尚未被研究。在这个五年提案中,我们将确定什么
分子信号导致大声的声音诱导周细胞迁移远离毛细血管及其表型
变化。我们还将确定是否移植新鲜周细胞,例如新周细胞(源自
新生小鼠)对噪声损伤的耳蜗进行修复可以修复因大声声音损伤的微血管并恢复血管
功能。每个目标的成功将不可避免地导致新的保护性和恢复性措施的开发
耳蜗正常血流的治疗——听力保留或/和恢复的关键基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Xiaorui Shi其他文献
Xiaorui Shi的其他文献
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{{ truncateString('Xiaorui Shi', 18)}}的其他基金
The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function
耳蜗周细胞及周细胞相关血管病理对听力功能的影响
- 批准号:
10553675 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function
耳蜗周细胞及周细胞相关血管病理对听力功能的影响
- 批准号:
10116361 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function
耳蜗周细胞及周细胞相关血管病理对听力功能的影响
- 批准号:
10327721 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
Strial vascular pathology from acoustic trauma
声损伤引起的心房血管病理学
- 批准号:
10174903 - 财政年份:2017
- 资助金额:
$ 42.54万 - 项目类别:
Perivascular macrophages endothelial interactions at the blood labyrinth barrier
血管周围巨噬细胞在血迷路屏障处的内皮相互作用
- 批准号:
8500225 - 财政年份:2012
- 资助金额:
$ 42.54万 - 项目类别:
Perivascular macrophages endothelial interactions at the blood labyrinth barrier
血管周围巨噬细胞在血迷路屏障处的内皮相互作用
- 批准号:
8386152 - 财政年份:2012
- 资助金额:
$ 42.54万 - 项目类别:
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
- 批准号:
8079462 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
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
- 批准号:
8664362 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
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
- 批准号:
8471544 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
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