Strial vascular pathology from acoustic trauma
Strial vascular pathology from acoustic trauma
批准号:
10174903
负责人:
Xiaorui Shi
金额:
$39.16万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-07-01 至 2023-06-30
关键词:
3-DimensionalAcoustic TraumaAffectAfferent NeuronsAgingAnimalsAuditoryAuditory ThresholdBasement membraneBiologicalBloodBlood VesselsBlood capillariesBlood flowBrainBromodeoxyuridineCaliberCardiologyCell LineCellsClinicalCochleaCommunicationConfocal MicroscopyConsumptionDevelopmentDiseaseEarEdemaElectron MicroscopyEndothelial CellsEnergy SupplyExposure toExtravasationFailureFoundationsFunctional disorderGene DeliveryGoalsGrowth FactorHair CellsHealthHearingHearing problemHeartHormonesHumanHypoxiaImmunophenotypingImpairmentIn VitroIndividualInfarctionInjuryKidney DiseasesLabelLabyrinthLateralLeadLifeLigandsLoudnessMaintenanceMediatingMembrane ProteinsMesenchymalMetabolicModelingMolecularMusMyocardial InfarctionMyofibroblastNatural regenerationNeuronsNoiseNuclearOrganPDGFA genePathologicPathologyPericytesPhenotypePhysiologyPlatelet-Derived Growth Factor BPlatelet-Derived Growth Factor beta ReceptorPopulationProductionProliferatingPropertyProteinsRecoveryRegulationReporterResearchResidual stateResolutionRetinaRoleSensorySignal PathwaySignal TransductionSiteSocial isolationSourceStressStria VascularisStrokeStructureSudden DeafnessSystemTestingTissuesTransforming Growth Factor betaTransforming Growth FactorsTransgenic MiceTransplantationTraumaVascular DiseasesVascular blood supplyangiogenesisbaseblood perfusiondeafnessdensitydiabetic patientfeasibility testingfibrogenesishearing impairmenthearing preservationheart functionimprovedinhibitor/antagonistinjury and repairmatrigelmigrationneonatal micenetwork modelsneurotrophic factornovelnovel strategiespigment epithelium-derived factorplatelet-derived growth factor BBpreservationpreventprotein expressionreceptorrepairedrestorationsoundstem cellssuccesstherapeutic targetwound healing
中文摘要
项目总结
耳朵的能量供应对听力功能至关重要,因为耳朵是能量消耗最高的地方之一
器官。能量不足的原因可能是流向耳蜗的血液不足,从而导致广泛的
临床听力障碍,如响声引起的听力损失,与衰老有关的听力损失,以及突发性
耳聋,这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
和社会孤立。我们认为,在听力功能丧失后成功修复和再生
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更广泛研究的一部分,但具体是
重点研究了大声音引起的侧壁微循环障碍时发生的周细胞病理。
周细胞是一种多能间充质样细胞,主要位于微血管上。的正常功能
周细胞对血流调节、血管完整性、血管生成和组织纤维化具有重要作用。周细胞
病理与许多器官疾病密切相关,如中风、心脏病和视网膜。
失败了。周细胞靶向治疗已被认为是许多临床上治疗此类疾病的新方法。
疾病。耳蜗周细胞对损伤非常脆弱和敏感,但对调节至关重要。
维持耳蜗血流量,维持血管纹血迷路屏障的紧密性。更多
具体地说,它们对压力高度敏感,比如声音创伤。一旦暴露在响亮的声音中,
耳蜗周细胞的生物学特性发生了显著的变化,但其分子机制
强调这些变化尚未得到研究。在这个五年计划中,我们将确定
分子信号导致强声诱导的周细胞离开毛细血管及其表型
改变。我们还将确定是否移植新鲜的周细胞,如新周细胞(来源于
新生小鼠)到噪声损伤的耳蜗可以修复响声损伤的微血管和恢复血管
功能。每一个目标的成功都必然会导致新的保护性和恢复性的发展
正常的耳蜗血流量的治疗--听力保护或/和恢复的关键基础。
英文摘要
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.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function
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批准号:10553675
-
项目类别:
-
资助金额:$46.26万
-
财政年份:2020
-
负责人:Xiaorui Shi
-
依托单位:
The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function
-
批准号:10116361
-
项目类别:
-
资助金额:$37.35万
-
财政年份:2020
-
负责人:Xiaorui Shi
-
依托单位:
The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function
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批准号:10327721
-
项目类别:
-
资助金额:$38.93万
-
财政年份:2020
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负责人:Xiaorui Shi
-
依托单位:
Cochlear angiogenesis
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批准号:9298262
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项目类别:
-
资助金额:$23.1万
-
财政年份:2017
-
负责人:Xiaorui Shi
-
依托单位:
Strial vascular pathology from acoustic trauma
-
批准号:9383753
-
项目类别:
-
资助金额:$42.54万
-
财政年份:2017
-
负责人:Xiaorui Shi
-
依托单位:
Perivascular macrophages endothelial interactions at the blood labyrinth barrier
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批准号:8500225
-
项目类别:
-
资助金额:$18.29万
-
财政年份:2012
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负责人:Xiaorui Shi
-
依托单位:
Perivascular macrophages endothelial interactions at the blood labyrinth barrier
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批准号:8386152
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项目类别:
-
资助金额:$23.1万
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财政年份:2012
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负责人:Xiaorui Shi
-
依托单位:
Fibrovascular coupling in the cochlea and pericyte recruitment after noise
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批准号:8079462
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项目类别:
-
资助金额:$37.27万
-
财政年份:2010
-
负责人:Xiaorui Shi
-
依托单位:
Fibrovascular coupling in the cochlea and pericyte recruitment after noise
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批准号:8664362
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项目类别:
-
资助金额:$37.27万
-
财政年份:2010
-
负责人:Xiaorui Shi
-
依托单位:
Fibrovascular coupling in the cochlea and pericyte recruitment after noise
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批准号:8471544
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项目类别:
-
资助金额:$35.4万
-
财政年份:2010
-
负责人:Xiaorui Shi
-
依托单位:
Fibrovascular coupling in the cochlea and pericyte recruitment after noise
-
批准号:8274722
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项目类别:
-
资助金额:$37.27万
-
财政年份:2010
-
负责人:Xiaorui Shi
-
依托单位:
The role of cochlear pericytes in control of cochlear microcirculation
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批准号:7856872
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项目类别:
-
资助金额:$5.69万
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财政年份:2009
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负责人:Xiaorui Shi
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依托单位:
The role of cochlear pericytes in control of cochlear microcirculation
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批准号:7386919
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项目类别:
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资助金额:$15.4万
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财政年份:2007
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负责人:Xiaorui Shi
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依托单位:
The role of cochlear pericytes in control of cochlear microcirculation
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批准号:7505437
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项目类别:
-
资助金额:$15.4万
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财政年份:2007
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负责人:Xiaorui Shi
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依托单位:
The role of cochlear pericytes in control of cochlear microcirculation
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批准号:7666050
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项目类别:
-
资助金额:$15.4万
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财政年份:2007
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负责人:Xiaorui Shi
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依托单位:
海外基金