A cellular basis for neurogenic orthostatic hypotension
神经源性直立性低血压的细胞基础
基本信息
- 批准号:8960461
- 负责人:
- 金额:$ 25.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-15 至 2017-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAgeAnimalsAreaBaroreflexBehavioralBlood PressureBrainBrain StemBrainstem VertigoCardiovascular systemCellsCerebrumClinical ResearchComplexConsensusDiseaseDizzinessElderlyEquilibriumExpectancyFOS ProteinFOS geneFeedbackFemaleForce of GravityFoundationsGenesGlutamatesHeadHomeostasisHumanImmediate-Early GenesInjection of therapeutic agentLabelLesionLinkMapsMediatingMedicalModelingMultiple System AtrophyMusNerveNerve DegenerationNeuromodulatorNeuronsNoseNuclearNucleus solitariusOrthostatic HypotensionParkinson DiseasePathway interactionsPatientsPerfusionPhysiologicalPilot ProjectsPositioning AttributePosturePressoreceptorsProteinsQuality of lifeRattusReflex actionReportingResearchRodent ModelRouteSignal TransductionStimulusSyncopeSystemTestingTissuesTracerVascular blood supplyVertigoWorkagedbaseblood pressure regulationfall riskfallsfeedingmalenervous system disorderneuroprotectionpituitary adenylate cyclase activating polypeptidepublic health relevanceresponsesexyoung adult
项目摘要
DESCRIPTION (provided by applicant): In humans, orthostatic hypotension (OH) is defined as a fall in blood pressure of at least 20/10 (systolic/diastolic) mmHg within three minutes of standing or during head-up tilt. It occurs in a wide variety of medical conditions, including neurologic disorders. Neurogenic OH is common in patients with dizziness, vertigo, brainstem lesions, and diseases such as multiple system atrophy and Parkinson's disease. Clinical studies indicate that one cause of neurogenic OH may be vestibular system hypofunction, particularly involving vestibulo-sympathetic reflex pathways. Support for this derives from numerous studies in humans and experimental animals that provide clear evidence for a functional link between the vestibular system and blood pressure control. Both vestibular system disorders (e.g. balance) and OH are more prevalent and severe in the elderly. This exploratory project uses an aged rat model to study one putative cellular alteration underlying OH. Pituitary adenylate cyclase-activating peptide (PACAP) is a neuromodulator involved in a wide range of physiological functions including cardiovascular control and neuroprotection. Recent preliminary studies indicate that PACAP is normally present in rat vestibular neurons, and that this expression is severely altered in aged animals with behavioral signs of OH. The present proposal seeks to determine, in both sexes, whether OH in aged rats is associated with degeneration of PACAP-containing neurons of the vestibulo-sympathetic reflex pathway. Aim 1 is to assess blood pressure changes in young-adult and aged male and female rats in response to sinusoidal galvanic vestibular stimulation and nose-up tilt, both of which activate the vestibulo- sympathetic reflex. We hypothesize that blood pressure will decrease in most aged rats, but few young-adults, establishing a rodent model of orthostatic hypotension. Aim 2 is to compare FluoroJade C labeling, which identifies degenerating neurons, in PACAP-positive vestibulo-sympathetic reflex projection neurons in tissue from the physiologically characterized rats studied in Aim 1. The retrograde tracer FluoroGold will be used to identify the projections, and cFos labeling will be used to verify that the neurons are activated by the stimulus. We hypothesize that OH correlates with degeneration of PACAP-containing vestibular neurons of the vestibulo-sympathetic reflex pathway. If successful, this project will provide the foundation for a comprehensive study addressing the cellular bases for the decline in vestibulo-sympathetic function in the elderly.
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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Gay R Holstein其他文献
Gay R Holstein的其他文献
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{{ truncateString('Gay R Holstein', 18)}}的其他基金
Chemoanatomic changes associated with aging in vestibulo-sympathetic pathways
与前庭交感神经通路衰老相关的化学解剖学变化
- 批准号:
8107476 - 财政年份:2010
- 资助金额:
$ 25.43万 - 项目类别:
Chemoanatomic changes associated with aging in vestibulo-sympathetic pathways
与前庭交感神经通路衰老相关的化学解剖学变化
- 批准号:
8005718 - 财政年份:2010
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
7859442 - 财政年份:2009
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
7844551 - 财政年份:2009
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
8463844 - 财政年份:2008
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
8662741 - 财政年份:2008
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
7467791 - 财政年份:2008
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
7570038 - 财政年份:2008
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
8115655 - 财政年份:2008
- 资助金额:
$ 25.43万 - 项目类别:
Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways
前庭交感神经通路的化学解剖学和突触学
- 批准号:
9306405 - 财政年份:2008
- 资助金额:
$ 25.43万 - 项目类别:
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