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
基本信息
- 批准号:10669786
- 负责人:
- 金额:$ 61.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2027-07-31
- 项目状态:未结题
- 来源:
- 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
项目摘要
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.
项目摘要/摘要
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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:
- 影响因子:0
- 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
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Susanne Janneke Van Veluw其他文献
Susanne Janneke Van Veluw的其他文献
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{{ truncateString('Susanne Janneke Van Veluw', 18)}}的其他基金
Perivascular Inflammation and Vascular Remodeling: A Common Cause of Hemorrhage in Cerebral Small Vessel Diseases?
血管周围炎症和血管重塑:脑小血管疾病出血的常见原因?
- 批准号:
10861499 - 财政年份:2023
- 资助金额:
$ 61.24万 - 项目类别:
Mechanisms of vasomotion-mediated perivascular clearance in cerebral amyloid angiopathy
脑淀粉样血管病血管舒缩介导的血管周围清除机制
- 批准号:
10518909 - 财政年份:2022
- 资助金额:
$ 61.24万 - 项目类别:
Unraveling the mechanisms of microhemorrhages in cerebral amyloid angiopathy
揭示脑淀粉样血管病微出血的机制
- 批准号:
10406382 - 财政年份:2018
- 资助金额:
$ 61.24万 - 项目类别:
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