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: 3401074
• 负责人: DIXON M MOODY
• 金额: $ 32.95万
• 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 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3401074
• 关键词: Pongidae; aging; basal ganglia; cerebral aneurysm; cerebrovascular disorders; cerebrovascular occlusions; histochemistry /cytochemistry; histopathology; human tissue; hypertension; image processing; infarct; laboratory rat; medulla oblongata; mesencephalon; microcirculation; spinal cord; stress proteins

This project proposes to 1) establish the relation of vascular disease to leukoaraiosis in the deep brain white matter in hypertensive and elderly humans and to correlate leukoaraiosis with the 70,000 Dalton stress protein (SP70) accumulation (a new molecular indicator of neurons and glia at risk); and 2) determine the etiology of the ubiquitous microemboli found in brains following cardiac surgery, and, with SP70, their significance. First problem: It is hypothesized that certain abnormal magnetic resonance (MR) are associated with intraparenchymal arterial/olar 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. Furthermore, the conclusions reached by this research might revise downward the stage of carotid stenosis at which surgical intervention is indicated. Second problem: At least 79 % of patients will have mild, moderate or severe intellectual dysfunction following surgery assisted by cardiopulmonary bypass (CPB). Although 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 cardiac surgery. Recently, microemboli have been found in autopsy brains shortly after CPB with the alkaline phosphatase (AP) method of vascular staining. The emboli range in size from 10 (mu)m to 40 (mu)m, a size that lodges in the smallest vessels of the microvasculature, and they have been found in numbers (Up to 10[6]) that might be expected to cause subtle neurological dysfunction. The outcome of surgery requiring CPB may be improved if these microemboli can be eliminated, but first their etiology must be established. Three cohorts will be studied: 1) hypertensives and elderly normotensives, and 2) postcardiac surgery patients. First project: postmortem MR will be performed on fresh autopsy brain slices. Protocol areas will be histochemically stained with the AP technique to facilitate examination of the microvasculature from the brain surface for the entire vascular length lesion to be investigated. Previous pathological correlations of deep abnormal MR signals 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 common MR imaging abnormalities. Second project: post CPB autopsy brains will have the AP microvascular stain; emboli will be identified and related to the site of appearance of a new molecular indicator of biological stress (SP70). and the identity of the embolic established.

该项目建议1）建立血管疾病之间的关系 高血压和脑深部白质脑白质疏松症 老年人并将脑白质疏松症与 70,000 道尔顿联系起来 应激蛋白（SP70）积累（神经元的新分子指标 和处于危险中的神经胶质细胞）； 2）确定普遍存在的病因 心脏手术后大脑中发现微栓子，并且使用 SP70， 他们的意义。 第一个问题：假设某些异常磁 共振 (MR) 与实质内动脉/OLA 相关 最终影响是血液运输慢性减少的疾病 容量。 这种慢性灌注不足可能会因颈椎病而加剧。 颈动脉粥样硬化。 为什么重要：当这些 MR 异常时， 通常是更严重疾病的先兆，一旦发现，应予以护理 在考虑治疗或任何其他治疗时对这些人进行锻炼 可能降低血压或脉压的干预措施。 此外， 这项研究得出的结论可能会向下修正 颈动脉狭窄，需要手术干预。 第二个问题：至少79%的患者会出现轻度、中度或 手术后严重智力障碍 体外循环（CPB）。 虽然似乎是病因 导致这种大脑功能障碍，几乎没有客观证据证实 使用最新的心脏检查技术报告存在栓塞 外科手术。 最近，尸检大脑中很快发现了微栓子 CPB后用碱性磷酸酶（AP）法进行血管染色。 栓子的尺寸范围为 10 (μ) m 至 40 (μ) m，该尺寸可容纳 在微脉管系统的最小血管中，人们发现了它们 数量（最多 10[6]）可能会导致微妙的 神经功能障碍。需要 CPB 的手术结果可能是 如果可以消除这些微栓塞，情况会有所改善，但首先要消除它们的病因 必须成立。 将研究三个队列：1）高血压和老年人 血压正常的患者，以及 2) 心脏手术后的患者。 第一个项目： 尸检 MR 将在新鲜尸检脑切片上进行。 协议 区域将用 AP 技术进行组织化学染色，以促进 检查整个大脑表面的微血管 待研究的血管长度病变。 既往病理性 仅研究了大脑中深层异常 MR 信号的相关性 直接异常区域的血管和神经纤维。 据信 拟议的研究将添加重要的预测信息 常见的磁共振成像异常。第二个项目：体外循环后尸检大脑 会有AP微血管染色；栓子将被识别并 与新分子指示剂的出现位点有关 生物应激（SP70）。并确定栓塞的身份。