Blood-Brain Barrier Dysfunction and Brain Injury in Heart Failure

心力衰竭时的血脑屏障功能障碍和脑损伤

基本信息

  • 批准号:
    9297116
  • 负责人:
  • 金额:
    $ 48.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-09-12 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Heart failure (HF) patients show brain injury in regions which control the autonomic (insular lobes), cognition (hippocampus, frontal cortex), and breathing (cerebellum) functions. Abnormalities in these sites are associated with symptoms which are linked to increased morbidity and mortality and decreased quality of life in HF. However, the underlying cause of brain injury in these areas in HF is unclear. Alteration in blood- brain barrier (BBB) function is a potential cause of brain damage in HF, as functional changes in the BBB are associated with neural injury in other diseases. However, there are no published reports of BBB changes in HF or regarding any association between BBB function and brain damage in this condition. Using non-invasive brain magnetic resonance imaging (MRI) procedures, our preliminary studies are the first to report BBB abnormalities (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures) in HF and that these BBB changes are associated with brain injury (as examined by diffusion tensor imaging based mean diffusivity [MD], an MRI measure of tissue integrity) in the insular lobes, hippocampus, frontal cortices, and cerebellar regions in HF subjects compared to controls. However, while promising, the sample size in this preliminary study was quite small and did not allow us to control for important covariates, such as age and gender. Therefore, the specific aims of this proposal are to: 1) compare global BBB function (calculated from diffusion-weighted pCASL) between HF and age- and gender-matched control subjects; 2) compare regional brain injury (assessed by MD) in the insular lobes, hippocampus, frontal cortices, and cerebellum between HF and age- and gender-matched healthy controls; 3) examine the relationship between altered BBB function (as indicated by diffusion-weighted pCASL data) and insular, hippocampal, frontal, and cerebellar injury (as indicated by MD measures) in HF patients. In summary, HF patients show significant regional brain injury in areas that control autonomic, cognitive, and breathing functions. A potential cause of this brain injury may be alterations in the BBB function. Abnormal BBB activity has not been reported previously in HF, but our preliminary studies have shown that BBB function is compromised and that this alteration is associated with brain injury in areas which control autonomic, cognitive, and breathing functions. The proposed study will examine global BBB function, assess regional tissue injury, and evaluate the relationships between BBB function and brain injury. Information from this study has the potential to disclose the processes contributing to brain injury in HF. Thus, it has important implications on identification of effectve treatments for HF by repairing BBB function, as used in other conditions (such as stroke), which could dramatically improve the mortality, morbidity, and quality of life in this high risk patient population.
DESCRIPTION (provided by applicant): Heart failure (HF) patients show brain injury in regions which control the autonomic (insular lobes), cognition (hippocampus, frontal cortex), and breathing (cerebellum) functions. Abnormalities in these sites are associated with symptoms which are linked to increased morbidity and mortality and decreased quality of life in HF. However, the underlying cause of brain injury in these areas in HF is unclear. Alteration in blood- brain barrier (BBB) function is a potential cause of brain damage in HF, as functional changes in the BBB are associated with neural injury in other diseases. However, there are no published reports of BBB changes in HF or regarding any association between BBB function and brain damage in this condition. Using non-invasive brain magnetic resonance imaging (MRI) procedures, our preliminary studies are the first to report BBB abnormalities (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures) in HF and that these BBB changes are associated with brain injury (as examined by diffusion tensor imaging based mean diffusivity [MD], an MRI measure of tissue integrity) in the insular lobes, hippocampus, frontal cortices, and cerebellar regions in HF subjects compared to controls. However, while promising, the sample size in this preliminary study was quite small and did not allow us to control for important covariates, such as age and gender. Therefore, the specific aims of this proposal are to: 1) compare global BBB function (calculated from diffusion-weighted pCASL) between HF and age- and gender-matched control subjects; 2) compare regional brain injury (assessed by MD) in the insular lobes, hippocampus, frontal cortices, and cerebellum between HF and age- and gender-matched healthy controls; 3) examine the relationship between altered BBB function (as indicated by diffusion-weighted pCASL data) and insular, hippocampal, frontal, and cerebellar injury (as indicated by MD measures) in HF patients. In summary, HF patients show significant regional brain injury in areas that control autonomic, cognitive, and breathing functions. A potential cause of this brain injury may be alterations in the BBB function. Abnormal BBB activity has not been reported previously in HF, but our preliminary studies have shown that BBB function is compromised and that this alteration is associated with brain injury in areas which control autonomic, cognitive, and breathing functions. The proposed study will examine global BBB function, assess regional tissue injury, and evaluate the relationships between BBB function and brain injury. Information from this study has the potential to disclose the processes contributing to brain injury in HF. Thus, it has important implications on identification of effectve treatments for HF by repairing BBB function, as used in other conditions (such as stroke), which could dramatically improve the mortality, morbidity, and quality of life in this high risk patient population.

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)

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Rajesh Kumar其他文献

Rajesh Kumar的其他文献

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{{ truncateString('Rajesh Kumar', 18)}}的其他基金

Thiamine Intervention and Cognition in Older Adults Undergoing Coronary Artery Bypass Grafting- A Randomized Clinical Trial
接受冠状动脉搭桥术的老年人的硫胺素干预和认知——一项随机临床试验
  • 批准号:
    10811014
  • 财政年份:
    2023
  • 资助金额:
    $ 48.27万
  • 项目类别:
Brain Metabolites, Brain Antioxidant, and Cerebral Blood Flow Deficits in Single Ventricle Heart Disease
单心室心脏病中的脑代谢物、脑抗氧化剂和脑血流缺陷
  • 批准号:
    10644553
  • 财政年份:
    2023
  • 资助金额:
    $ 48.27万
  • 项目类别:
Brain Changes in Pediatric Obstructive Sleep Apnea
小儿阻塞性睡眠呼吸暂停的大脑变化
  • 批准号:
    10468277
  • 财政年份:
    2021
  • 资助金额:
    $ 48.27万
  • 项目类别:
Brain Changes in Pediatric Obstructive Sleep Apnea
小儿阻塞性睡眠呼吸暂停的大脑变化
  • 批准号:
    10218463
  • 财政年份:
    2021
  • 资助金额:
    $ 48.27万
  • 项目类别:
Cerebral Artery Integrity Linked to Brain Injury and Cognition in Congenital Heart Disease
脑动脉完整性与先天性心脏病的脑损伤和认知有关
  • 批准号:
    9157665
  • 财政年份:
    2016
  • 资助金额:
    $ 48.27万
  • 项目类别:
Cerebral Artery Integrity Linked to Brain Injury and Cognition in Congenital Heart Disease
脑动脉完整性与先天性心脏病的脑损伤和认知有关
  • 批准号:
    9337504
  • 财政年份:
    2016
  • 资助金额:
    $ 48.27万
  • 项目类别:
Blood-Brain Barrier Deficit and Brain Injury in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停中的血脑屏障缺陷和脑损伤
  • 批准号:
    8887911
  • 财政年份:
    2015
  • 资助金额:
    $ 48.27万
  • 项目类别:
Blood-Brain Barrier Deficit and Brain Injury in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停中的血脑屏障缺陷和脑损伤
  • 批准号:
    9038446
  • 财政年份:
    2015
  • 资助金额:
    $ 48.27万
  • 项目类别:
Blood-Brain Barrier Dysfunction and Brain Injury in Heart Failure
心力衰竭时的血脑屏障功能障碍和脑损伤
  • 批准号:
    8926474
  • 财政年份:
    2014
  • 资助金额:
    $ 48.27万
  • 项目类别:
Brain Axonal Injury in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停引起的脑轴突损伤
  • 批准号:
    8692590
  • 财政年份:
    2012
  • 资助金额:
    $ 48.27万
  • 项目类别:
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