Global Blood-Brain Barrier Disruption and Post-Stroke Cognitive Decline

全球血脑屏障破坏和中风后认知能力下降

基本信息

批准号：
10598120
负责人：
RICHARD LEIGH
金额：
$ 62.06万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2022-04-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598120
关键词：
Acceleration Acute Affect Alzheimer&apos s disease related dementia Biological Markers Blood Blood - brain barrier anatomy Blood Tests Blood flow Brain Brain scan Caregivers Cerebrum Chronic Clinical Contrast Media Dementia Development Disease Epidemiology Evaluation Event Functional disorder Gadolinium Goals Health system Healthcare Systems Homeostasis Hospitals Hypoxia Image Impaired cognition Impairment Incidence Individual Inflammatory Inflammatory Response Injury Ischemia Ischemic Stroke Link Longitudinal Studies MRI Scans Magnetic Resonance Imaging Maps Measurement Measures Mediating Methods Microvascular Dysfunction Monitor Pathogenesis Pathology Patients Perfusion Permeability Persons Prevalence Process Public Health Research Resolution Risk Role Secondary Prevention Serial Magnetic Resonance Imaging Signal Transduction Societies Sterility Stroke Techniques Testing Therapeutic Therapeutic Trials Time Translating Vascular Dementia Vascular Diseases Water White Matter Hyperintensity acute stroke aging population arterial spin labeling biomarker development blood-brain barrier crossing blood-brain barrier disruption blood-brain barrier permeabilization brain tissue cardiovascular risk factor clinical imaging cognitive testing cohort epidemiology study imaging study improved novel novel marker patient subsets perfusion imaging post stroke post stroke cognitive impairment predictive marker recruit relapse prevention response serial imaging stroke patient targeted biomarker time use tissue injury vascular cognitive impairment and dementia vascular factor vascular risk factor white matter

项目摘要

Project Summary/Abstract This study is focused on expanding our understanding of post-stroke cognitive impairment and dementia (PSCID). Studies have found that patients who suffer a stroke are at increased risk for developing subsequent cognitive decline. While this has been demonstrated epidemiologically, the mechanism by which this occurs is not known. PSCID is a form of vascular cognitive impairment and dementia (VCID). VCID has been linked to progressive changes in the white matter, referred to as white matter hyperintensities (WMH), that are readily seen on magnetic resonance imaging (MRI). It has been hypothesized that disruption of the blood-brain barrier (BBB) precedes the development of WMH. Thus, imaging the BBB may be a way to determine who is at risk for developing VCID. It is the central hypothesis of this proposal that PSCID is due to acceleration of VCID brought on by the acute ischemic event and is characterized by global disruption of the BBB which precedes the development of WMH. Thus we aim to: 1) Test if BBB disruption detected on routine clinical MRI scans of the brain is predictive of PSCID, 2) Study the mechanism of progressive WMH in post-stroke patients using serial research MRI scans to measure BBB disruption of normal appearing white matter before it progresses to WMH, and 3) Translate a novel MRI method into the clinical setting that uses arterial spin labeling (ASL) to measure BBB disruption without the administration of exogenous contrast. To achieve these objectives patients will be recruited from hospitals in the Johns Hopkins Health System. Patients will be followed with serial cognitive testing to detect cognitive decline over a 3-year period. BBB measurements will be extracted from the MRI scans done at the time of the evaluation for acute stroke. A subset of patients will be followed with serial research MRIs. Research MRIs will be used to track the progression of NAWM to WMH and its relationship to BBB disruption. These research MRIs will also implement a novel ASL method for measuring BBB permeability to determine if this method could be used instead of contrast-based methods. The long-term goal of this research is to validate a biomarker for the pathogenesis of PSCID such that patients at risk can be identified for therapeutic trials and potential therapeutics can be screened for their effect on the pathology.

项目概要/摘要这项研究的重点是扩大我们对中风后认知障碍的理解痴呆症（PSCID）。研究发现，中风患者罹患中风的风险增加随后出现认知能力下降。虽然这已在流行病学上得到证实，发生这种情况的机制尚不清楚。 PSCID 是血管认知的一种形式损伤和痴呆（VCID）。 VCID 与白色的渐进性变化有关物质，称为白质高信号（WMH），在磁力上很容易看到磁共振成像（MRI）。据推测，血脑屏障被破坏 (BBB) 先于 WMH 的发展。因此，对 BBB 进行成像可能是确定的一种方法谁有患 VCID 的风险。该提案的中心假设是 PSCID 是由于急性缺血事件引起的 VCID 加速，其特点是全球 BBB 的破坏先于 WMH 的发展。因此，我们的目标是：1）测试 BBB 是否大脑常规临床 MRI 扫描检测到的破坏可预测 PSCID，2) 研究使用系列研究 MRI 扫描来研究中风后患者进行性 WMH 的机制在进展为 WMH 之前测量正常白质的 BBB 破坏，以及 3) 将一种新颖的 MRI 方法转化为临床环境，使用动脉自旋标记 (ASL) 无需施用外源性造影剂即可测量 BBB 破坏。为了实现这些目标将从约翰霍普金斯大学卫生系统的医院招募患者。患者随后将进行一系列认知测试，以检测三年内认知能力的下降。血脑屏障测量值将从评估急性发作时进行的 MRI 扫描中提取中风。一部分患者将接受系列研究 MRI 随访。研究 MRI 将用于追踪 NAWM 向 WMH 的进展及其与 BBB 破坏的关系。这些研究 MRI 还将实施一种新颖的 ASL 方法来测量 BBB 渗透性确定是否可以使用此方法来代替基于对比度的方法。长期目标这项研究的目的是验证 PSCID 发病机制的生物标志物，以便患者可以识别治疗试验的风险，并可以筛选潜在的治疗方法对病理的影响。