Signals and targets underlying mechanisms for neurovascular coupling in the brain
大脑神经血管耦合的信号和目标潜在机制
基本信息
- 批准号:7806456
- 负责人:
- 金额:$ 29.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-05-01 至 2013-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcidsAddressAffectArtsAstrocytesBlood VesselsBrainCalciumCalcium-Activated Potassium ChannelCellsCerebral cortexCerebrovascular CirculationCerebrumChronicCommunicationCouplingDiseaseEventGlucoseGlutamatesHealthHyperemiaHypertensionIonsLearningLightLinkMediatingMediator of activation proteinMetabolicMicrocirculationMigraineMuscle CellsNatureNeurogliaNeuronsNeurotransmittersOxygenPathologyPatternPhysiologicalPotassiumPotassium ChannelPreparationProcessProductionPropertyRattusResearch PersonnelSignal PathwaySignal TransductionSliceSmooth Muscle MyocytesStrokeSynapsesVasodilationVasodilator AgentsWorkarteriolecell typeextracellulargamma-Aminobutyric Acidinnovationinsightintercellular communicationlarge-conductance calcium-activated potassium channelsmultidisciplinaryneurovascular unitprogramsrelating to nervous systemresponsespreading depressionvasoconstriction
项目摘要
DESCRIPTION (provided by the applicant): The main focus of this study is to characterize the cellular mechanisms underlying functional hyperemia in the cerebral cortex. Functional hyperemia occus as a function of the communication between neurons, astrocytes and the cerebral microcirculation. Disturbances in the signaling pathways leading to the proper hyperemic response have been linked to a number of pathologies including hypertension, stroke, migraine, and spreading depression, to mention a few. Although functional hyperemia occurs within seconds, the underlying mechanisms mediating such rapid signaling response are still to be defined. This project will address three major aims: First, to determine if astrocytes are intermediaries in neurovascular coupling (Aim 1). Second, to determine if the mechanism by which astrocytes communicate with parenchymal arterioles, to induce vasodilation, results from the rapid activation of Ca2+-activated K+ (BK) channels and the release of K+ into the narrow space between the astrocytic endfoot and vascular cells. Also to determine if epoxyeicosatrienoic acids contribute to the activation of BK channels in the astrocytic endfeet amplifying the signaling communication between astrocytes and blood vessels (Aim 2). Third, to determine if both functional and structural alterations occur in the neurovascular unit during hypertension (Aim 3). We hypothesize that following neuronal stimulation, the rise in intracellular Ca2+ in the astrocytes activated BK channels in astrocytic endfeet resulting in the rapid release of K+ (a strong vasodilator) in the space between the endfoot and the vascular cells. The rise in Ca2+ also increases the production of epoxyeicosatrienoic acids which act on BK channels in the astrocytic endfeet further activating these channels. Because functional and anatomical changes in neurons, asttrocytes and parenchymal arterioles are linked to one another, an understanding of the modes of communication within the neural-glial-vascular network under physiological conditions will provide insights on pathologies, such as hypertension, which affect one or more of these three cellular components constituting the neurovascular unit.
描述(由申请方提供):本研究的主要重点是表征大脑皮层功能性充血的细胞机制。功能性充血是神经元、星形胶质细胞和脑微循环之间的通讯的功能。导致适当充血反应的信号传导通路的紊乱与许多病理学有关,包括高血压、中风、偏头痛和扩散性抑郁症等。虽然功能性充血在几秒钟内发生,但介导这种快速信号反应的潜在机制仍有待确定。这个项目将解决三个主要目标:第一,以确定星形胶质细胞是否在神经血管耦合的中介(目标1)。第二,确定星形胶质细胞与实质小动脉沟通以诱导血管舒张的机制是否是由于Ca 2+激活的K+(BK)通道的快速激活和K+释放到星形胶质细胞终足和血管细胞之间的狭窄空间中。还确定环氧二十碳三烯酸是否有助于激活星形胶质细胞终足中的BK通道,从而放大星形胶质细胞和血管之间的信号传递(目的2)。第三,确定高血压时神经血管单位是否发生功能和结构改变(目的3)。我们假设,神经元刺激后,星形胶质细胞内Ca 2+的上升激活BK通道星形胶质细胞endfoot导致快速释放K+(一种强血管扩张剂)之间的空间endfoot和血管细胞。Ca 2+的升高也增加了环氧二十碳三烯酸的产生,环氧二十碳三烯酸作用于星形胶质细胞末足中的BK通道,进一步激活这些通道。由于神经元、星形胶质细胞和实质小动脉的功能和解剖学变化相互关联,因此对生理条件下神经-胶质-血管网络内的通信模式的理解将提供对病理学的见解,例如高血压,其影响构成神经血管单元的这三种细胞组分中的一种或多种。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JESSICA A FILOSA其他文献
JESSICA A FILOSA的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JESSICA A FILOSA', 18)}}的其他基金
The impact of blood pressure variability on neurovascular function
血压变异性对神经血管功能的影响
- 批准号:
10745027 - 财政年份:2023
- 资助金额:
$ 29.4万 - 项目类别:
The impact of blood pressure variability on neurovascular function
血压变异性对神经血管功能的影响
- 批准号:
10419670 - 财政年份:2021
- 资助金额:
$ 29.4万 - 项目类别:
Inverse neurovascular coupling in the hypothalamus and its role in positive feedback regulation of Vasopressin neurons in health and disease
下丘脑的逆神经血管耦合及其在健康和疾病中加压素神经元正反馈调节中的作用
- 批准号:
10391639 - 财政年份:2021
- 资助金额:
$ 29.4万 - 项目类别:
Inverse neurovascular coupling in the hypothalamus and its role in positive feedback regulation of Vasopressin neurons in health and disease
下丘脑的逆神经血管耦合及其在健康和疾病中加压素神经元正反馈调节中的作用
- 批准号:
10531928 - 财政年份:2021
- 资助金额:
$ 29.4万 - 项目类别:
Clinically unscreened vasculo-glial-neuronal coupling is critical for physiological brain function
临床上未经筛选的血管-胶质-神经元耦合对于生理脑功能至关重要
- 批准号:
9884817 - 财政年份:2017
- 资助金额:
$ 29.4万 - 项目类别:
Clinically unscreened vasculo-glial-neuronal coupling is critical for physiological brain function
临床上未经筛选的血管-胶质-神经元耦合对于生理脑功能至关重要
- 批准号:
10117289 - 财政年份:2017
- 资助金额:
$ 29.4万 - 项目类别:
Clinically unscreened vasculo-glial-neuronal coupling is critical for physiological brain function
临床上未经筛选的血管-胶质-神经元耦合对于生理脑功能至关重要
- 批准号:
9442869 - 财政年份:2017
- 资助金额:
$ 29.4万 - 项目类别:
Clinically unscreened vasculo-glial-neuronal coupling is critical for physiological brain function
临床上未经筛选的血管-胶质-神经元耦合对于生理脑功能至关重要
- 批准号:
9311373 - 财政年份:2017
- 资助金额:
$ 29.4万 - 项目类别:
Signals and targets underlying mechanisms for neurovascular coupling in the brain
大脑神经血管耦合的信号和目标潜在机制
- 批准号:
7841408 - 财政年份:2009
- 资助金额:
$ 29.4万 - 项目类别:
Signals and targets underlying mechanisms for neurovascular coupling in the brain
大脑神经血管耦合的信号和目标潜在机制
- 批准号:
8059688 - 财政年份:2007
- 资助金额:
$ 29.4万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 29.4万 - 项目类别:
Research Grant