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

• 批准号: 10444660
• 负责人: RICHARD LEIGH
• 金额: $ 65.91万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/10444660
• 关键词: Acceleration; Acute; Affect; Alzheimer' 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; Imaging Techniques; Impaired cognition; Impairment; Incidence; Individual; Inflammatory; Inflammatory Response; Injury; 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; Recurrence; Research; Resolution; Risk; Role; Secondary Prevention; Serial Magnetic Resonance Imaging; Signal Transduction; Societies; Sterility; Stroke; Testing; Therapeutic; Therapeutic Trials; Time; Translating; Vascular Dementia; Vascular Diseases; Water; White Matter Hyperintensity; acute stroke; aging population; arterial spin labeling; base; 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 modality; imaging study; improved; novel; novel marker; patient subsets; perfusion imaging; post stroke; post stroke cognitive impairment; predictive marker; recruit; response; serial imaging; stroke patient; targeted biomarker; time use; tissue injury; vascular cognitive impairment and dementia; vascular factor; vascular risk factor; white matter

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.

项目总结/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（PSCID）。研究发现，中风患者患中风的风险增加， 导致认知能力下降虽然这已经在流行病学上得到证明， 发生这种情况的机制尚不清楚。PSCID是一种血管认知障碍， 痴呆症（VCID）。VCID与白色的渐进变化有关 物质，称为白色物质高强度（WMH），在磁共振成像上很容易看到。 磁共振成像（MRI）。有一种假说认为血脑屏障的破坏 (BBB)WMH的发展。因此，对血脑屏障进行成像可能是一种确定 有患VCID风险的人这是该提案的核心假设，即PSCID是由于 急性缺血性事件引起的VCID加速，其特征是 在WMH发展之前，血脑屏障被破坏。因此，我们的目标是：1）测试是否BBB 在常规临床脑部MRI扫描中检测到的破坏可预测PSCID，2）研究 脑卒中后患者进行性WMH的机制，使用系列研究MRI扫描， 在正常出现的白色物质进展为WMH之前测量其BBB破坏，以及3） 将一种新的MRI方法转化为使用动脉自旋标记（ASL）的临床环境， 在不给予外源性造影剂的情况下测量BBB破坏。实现这些 目标患者将从约翰霍普金斯卫生系统的医院招募。患者 随后将进行一系列认知测试，以检测3年内的认知能力下降。BBB 将从评价急性脑梗死时进行的MRI扫描中提取测量值， 中风一部分患者将接受系列研究MRI随访。研究MRI将是 用于跟踪NAWM到WMH的进展及其与BBB破坏的关系。这些 研究MRI还将实施一种新的ASL方法来测量BBB渗透性， 确定是否可以使用这种方法来代替基于对比度的方法。远景目标 这项研究的目的是验证PSCID发病机制的生物标志物， 可以识别治疗试验的风险，并筛选潜在的治疗方法， 对病理学的影响。