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 老年人的深脑白质中的白细胞病和 将白血病与热休克蛋白（HSP70）累积相关（a 神经元和神经胶质的新分子指标）； 2）确定 无处不在的外源性血管内的病因和意义 心肺旁路后的大脑中发现的材料（称为SCADS） （CPB）。 第一个问题：假设某些异常磁共振 （MR）信号与核内血管疾病有关 最终效应是血液运输能力的长期降低。这 颈颈颈会加剧慢性灌注不足 动脉粥样硬化。为什么重要：当这些先生异常时，通常是 鉴定出更严重疾病的预兆，应谨慎行事 在考虑治疗或任何干预措施时 可能会降低血液或脉压。 第二个问题：24-38％的患者将拥有永久性的轻度至重度 CPB辅助手术后的智力功能障碍。虽然 微栓塞似乎是引起这种大脑的病因学剂 功能障碍，几乎没有目的证据证实了栓子的存在 报道了CPB的最新技术。最近，Scads有 在CPB和碱性碱后不久，在尸检大脑中发现 血管染色的磷酸酶（AP）方法。 SCADS的大小从10 mu m至70 mu m，尺寸在最小的容器中。 微脉管系统，它们的数量（最多为10-6）可能 期望引起微妙的神经功能障碍，它们是 相信但没有证明是栓子。需要手术的结果 如果可以消除SCADS，则可以改善CPB，但首先是他们的病因 必须建立。 将研究这些队列：l）高血压和老年正常敏度； 2）CPB后患者； 3）经历了CPB的狗。第一个项目： 尸检脑切片的MR将识别白细胞病的区域。 协议区域将用AP技术在组织化学上染色 促进检查脑表面传入脉管系统 在整个长度上，要研究病变的静脉。 异常MR信号的先前病理相关性深处 大脑仅研究了立即异常的血管和神经肽 区域。据信，拟议的研究将增加大量 通用MR成像异常的预测信息。第二 项目：将按顺序研究CPB后的尸检和狗脑材料 确定元素组成（用激光微探针质量 光谱法），组织损伤程度（HSP70和微吸收）和 SCADS的起源。