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

项目摘要/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，并 痴呆(PSCID)。研究发现，中风患者患中风的风险增加。 发展为随后的认知衰退。虽然这一点已经在流行病学上得到了证明， 这种情况发生的机制尚不清楚。PSCID是血管认知的一种形式 损害和痴呆症(VCID)。VCID被认为与白人的渐进性变化有关 物质，称为白质高强度(WMH)，很容易在磁学上看到 磁共振成像(MRI)。据推测，血脑屏障的破坏 (BBB)先于WMH的发展。因此，对血脑屏障进行成像可能是确定 世卫组织面临发展为VCID的风险。这一提议的中心假设是PSCID应 由急性脑缺血事件引起的VCID加速，其特点是 在WMH发展之前的血脑屏障的破坏。因此，我们的目标是：1)测试血脑屏障 常规临床MRI脑部扫描检测到的干扰是PSCID的预测，2)研究 用系列研究MRI扫描研究卒中后患者进行性WMH的机制 在进展为WMH之前测量正常出现的白质的血脑屏障破坏，以及3) 将一种新的MRI方法转化为临床环境，使用动脉自旋标记(ASL)来 在不使用外源性对比剂的情况下测量血脑屏障中断。要实现这些目标 目的患者将从约翰霍普金斯卫生系统的医院招募。病人 随后将进行一系列认知测试，以检测为期3年的认知能力下降。BBB 测量结果将从评估急性发作时所做的MRI扫描中提取 卒中。一部分患者将接受一系列研究核磁共振检查。研究核磁共振将是 用于跟踪NAWM到WMH的进展及其与BBB中断的关系。这些 Research MRI还将实施一种新的ASL方法，用于测量BBB通透性 确定是否可以使用此方法来替代基于对比的方法。长期目标 这项研究的目的是验证PSCID发病机制的生物标记物，使患者在 可以确定治疗试验的风险，并可以筛选潜在的治疗药物 对病理的影响。

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.