BRAIN VASCULATURE IN LEUKOARAIOSIS AND CARDIAC SURGERY

白质疏松症和心脏手术中的脑血管

• 批准号: 2460501
• 负责人: DIXON M MOODY
• 金额: $ 54.39万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2460501
• 关键词: aging; alkaline phosphatase; cerebral degeneration; cerebrovascular disorders; dogs; embolism; heart /lung bypass; histochemistry /cytochemistry; human tissue; hypertension; iatrogenic disease; magnetic resonance imaging; mass spectrometry; microcirculation; stress proteins

This project proposes to 1) establish the relation of vascular disease to leukoaraiosis in the deep brain white matter in elderly humans and to correlate leukoaraiosis with heat shock protein (HSP70) accumulation (a new molecular indicator of neurons and glia at risk); and 2) determine the etiology and significance of the ubiquitous exogenous intravascular material (called SCADs) found in brains following cardiopulmonary bypass (CPB). First problem: It is hypothesized that certain abnormal magnetic resonance (MR) signals are associated with intraparenchymal vascular diseases whose ultimate effect is chronic reduction in blood transport capacity. This chronic hypoperfusion may be exacerbated by cervical carotid atherosclerosis. Why important: when these MR abnormalities, often the harbinger of more severe disease, are identified, care should be exercised in these individuals when contemplating therapy or any intervention that might decrease blood or pulse pressure. Second problem: 24-38% of patients will have permanent mild-to-severe intellectual dysfunction following surgery assisted by CPB. Although microemboli appear to be the etiologic agent causing this brain dysfunction, little objective evidence confirming the presence of emboli is reported with the most recent techniques of CPB. Recently, SCADs have been found in autopsy brains shortly after CPB with the alkaline phosphatase (AP) method of vascular staining. SCADs range in size from 10 mu m to 70 mu m, a size that lodges in the smallest vessels of the microvasculature, they have been found in numbers (up to 10-6) that might be expected to cause subtle neurological dysfunction and they are belIeved, but not proven, to be emboli. The outcome of surgery requiring CPB may be improved if SCADs can be eliminated, but first theIr etiology must be establIshed. These cohorts will be studied: l) hypertensives and elderly normotensives; 2) post-CPB patients; and 3) dogs who have undergone CPB. First project: MR of autopsy brain slices will identify areas with leukoaraiosis. Protocol areas will be histochemically stained with the AP technique to facilitate examination of the afferent vasculature at the brain surface for the entire length to and the veins from the lesion to be investigated. Previous pathological correlations of abnormal MR signals deep in the brain have studied only the vessels and neuropil in the immediate abnormal area. It is believed that the proposed study will add significant predictive information to this common MR imaging abnormality. Second project: post CPB autopsy and dog brain material will be studied in order to determine the elemental composition (with laser microprobe mass spectrometry), degree of tissue injury (HSP70 and microinfarcts), and genesis of SCADs.

该项目建议 1) 建立血管疾病与 老年人大脑深部白质的脑白质疏松症 脑白质疏松症与热休克蛋白 (HSP70) 积累相关（a 处于危险中的神经元和神经胶质细胞的新分子指标）； 2) 确定 普遍存在的外源性血管内病变的病因和意义 体外循环后大脑中发现的物质（称为 SCAD） （CPB）。 第一个问题：假设某些异常磁共振 (MR) 信号与实质内血管疾病相关，其 最终的影响是血液运输能力的慢性降低。这 颈动脉可能会加剧慢性灌注不足 动脉粥样硬化。为什么重要：当这些 MR 异常时，通常 发现更严重疾病的先兆，应予以小心 在这些人考虑治疗或任何干预措施时 可能会降低血压或脉压。 第二个问题：24-38%的患者会出现永久性的轻度至重度症状 体外循环辅助手术后智力障碍。虽然 微栓子似乎是导致这种大脑的病因 功能障碍，很少有客观证据证实栓塞的存在 使用最新的 CPB 技术进行报告。最近，SCAD 在用碱性体外循环后不久的尸检大脑中发现 血管染色的磷酸酶（AP）方法。 SCAD 的大小范围为 10 微米到70微米，这个尺寸可以容纳在最小的容器中 微血管系统中，已发现它们的数量（最多 10-6 个）可能 预计会引起微妙的神经功能障碍，并且它们是 相信但未证实是栓塞。手术结果要求 如果可以消除 SCAD，CPB 可能会得到改善，但首先是病因学 必须建立。 将研究这些人群： l) 高血压患者和血压正常的老年患者； 2) CPB后患者； 3) 接受过体外循环的狗。第一个项目： 尸检脑切片的磁共振将识别脑白质疏松的区域。 方案区域将使用 AP 技术进行组织化学染色，以 促进大脑表面传入脉管系统的检查 对于要研究的病变的整个长度和静脉。 先前异常 MR 信号深层的病理相关性 大脑只研究了直接异常的血管和神经纤维 区域。据信，拟议的研究将显着增加 这种常见的 MR 成像异常的预测信息。第二 项目：体外循环后尸检和狗脑材料将按顺序研究 确定元素成分（使用激光微探针质量 光谱测定法）、组织损伤程度（HSP70 和微梗死），以及 SCAD 的起源。