课题基金 / 基金详情

Mechanisms of Vasomotion-mediated Perivascular Clearance in Cerebral Amyloid Angiopathy

Mechanisms of Vasomotion-mediated Perivascular Clearance in Cerebral Amyloid Angiopathy
脑淀粉样血管病中血管舒缩介导的血管周围清除机制
批准号:
10669786
负责人:
Susanne Janneke Van Veluw
金额:
$61.24万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-08-01 至 2027-07-31
关键词:
Abeta clearanceAccelerationAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAmyloid beta-ProteinArteriesAutomobile DrivingBlood VesselsBlood capillariesBrainCalciumCell physiologyCellsCephalicCerebral Amyloid AngiopathyCerebral hemisphere hemorrhageCerebrospinal FluidCerebrovascular systemChronicCoupledCouplingDataDementiaDepositionDextransDiseaseDisease modelDrainage procedureEarly InterventionElderlyEventFrequenciesFunctional Magnetic Resonance ImagingFunctional disorderFutureGenesHemorrhageHigh PrevalenceHumanImageImaging TechniquesImmunotherapyImpaired cognitionImpairmentIndividualInjectionsIntercellular FluidInterventionLabelLeptomeningesLiteratureLobarMeasuresMediatingMetabolicMethodsModelingMusNutrientOxygenPathway interactionsPatientsPatternPhotic StimulationPhysiologicalPhysiologyPlayProcessPropertyResearchResolutionRestRiskRoleSeveritiesSmooth Muscle MyocytesSpeedSystemTechniquesTestingTimeTracerTransgenic MiceTranslationsVascular DiseasesVascular Smooth MuscleVisualWaste ProductsWorkabeta accumulationabeta depositionaging brainarterioleawakeblood oxygen level dependentbrain healthbrain tissuecerebrospinal fluid flowclinical diagnosisdesigndriving forceeffective therapyexperimental studyfluid flowhemodynamicsimprovedin vivoin vivo optical imaginginnovationmouse modelneuroimagingnew therapeutic targetnon-invasive imagingnoveloptical imagingoptogeneticsparticlepreservationpreventsingle-cell RNA sequencingsolutetherapeutic developmenttranscriptomicstranslational approachtwo photon microscopyvasomotionwasting

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中文摘要
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项目摘要/摘要
英文摘要
Project Summary / Abstract Title project: “Mechanisms of vasomotion-mediated perivascular clearance in cerebral amyloid angiopathy” The blood vessels in the brain play an important role in facilitating clearance of metabolic waste products. Impaired perivascular clearance of amyloid β (Aβ) has been implicated in the pathophysiology of cerebral amyloid angiopathy (CAA) and Alzheimer’s disease. However, fundamental unknows including the directionality and major driving forces of perivascular clearance remain, which has hampered the development of therapeutic strategies aimed at targeting the perivascular waste clearance system. Moreover, experimental observations in mice have remain largely unexplored in the human brain. Prior work from the applicant uncovered a role for vasomotion – slow spontaneous oscillations of arterioles generated by vascular smooth muscle cells (SMCs) – as a major driving force for perivascular clearance. This project will further zoom in on vasomotion and test the novel hypothesis that targeting vascular SMCs may provide an attractive approach to enhance vasomotion and thereby facilitate perivascular Aβ clearance. This project will use CAA as a model disease to test this hypothesis, as CAA is characterized by the gradual deposition of vascular Aβ, impaired perivascular clearance, SMC degeneration, and vascular dysfunction. The aims of this project are to further unravel the physiological basis of vasomotion-mediated perivascular clearance, to determine the effect of vascular Aβ accumulation on vasomotion and clearance, to explore the potential of enhancing low frequency arteriolar oscillations as an intervention strategy to successfully clear Aβ from the brain, and to measure the coupling between low frequency hemodynamics and fluid flow in the human brain. We will use a translational approach, utilizing optical imaging techniques in awake mice coupled with direct optogenetic stimulation of vascular SMCs, as well as fast functional MRI in human individuals with and without CAA. Successful completion of these aims will improve our understanding of the physiological basis of vasomotion-mediated perivascular clearance and provide much needed proof-of-concept data to support the potential of modulating low frequency arteriolar oscillations as an early intervention strategy to promote Aβ clearance from the brain.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Spontaneous vasomotion propagates along pial arterioles in the awake mouse brain like stimulus-evoked vascular reactivity.
自发血管舒缩沿着清醒小鼠大脑中的软脑膜小动脉传播,就像刺激引起的血管反应一样。
DOI: 10.1177/0271678x231152550
发表时间: 2023
期刊: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子: --
作者: [Munting,LeonP, Bonnar,Orla, Kozberg,MarielG, Auger,CorinneA, Hirschler,Lydiane, Hou,StevenS, Greenberg,StevenM, Bacskai,BrianJ, vanVeluw,SusanneJ]
通讯作者: vanVeluw,SusanneJ
Perivascular Inflammation and Vascular Remodeling: A Common Cause of Hemorrhage in Cerebral Small Vessel Diseases?
  • 批准号:
    10861499
  • 项目类别:
  • 资助金额:
    $77.65万
  • 财政年份:
    2023
  • 负责人:
    Susanne Janneke Van Veluw
  • 依托单位:
Mechanisms of vasomotion-mediated perivascular clearance in cerebral amyloid angiopathy
  • 批准号:
    10518909
  • 项目类别:
  • 资助金额:
    $61.51万
  • 财政年份:
    2022
  • 负责人:
    Susanne Janneke Van Veluw
  • 依托单位:
Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathy
  • 批准号:
    10406382
  • 项目类别:
  • 资助金额:
    $24.84万
  • 财政年份:
    2018
  • 负责人:
    Susanne Janneke Van Veluw
  • 依托单位:
海外基金