Hemodynamics and metabolism in stroke-prone spontaneously hypertensive rats before manifestation of brain infarcts
Hemodynamics and metabolism in stroke-prone spontaneously hypertensive rats before manifestation of brain infarcts
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DOI：
10.1097/00004647-199911000-00008
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发表时间：
1999-11-01
影响因子：
6.3
通讯作者：
Hossmann, KA
中科院分区：
文献类型：
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作者：
Mies, G;Hermann, D;Hossmann, KA
对易卒中（SHR-SP）和卒中抵抗的自发性高血压大鼠（SHR）的杂交后代进行基因组筛选，发现大鼠1号染色体上有一个STR 1基因座，该基因座与脑卒中的易感性相关，但与高血压无关。作者研究了这种遗传异常是否与脑中的血流动力学或代谢改变有关，这些改变可以在脑梗死表现之前检测到。从6周龄开始，给SHR-SP喂食高盐饮食以加速动脉高压。在12周龄时，动物出现功能性症状，并与年龄匹配的SHR阴性SHR-SP区分症状前和症状后的变化。大脑进行了研究，包括定量双示踪剂放射自显影CBF和脑蛋白质合成（CPS）的多参数成像;生物发光成像的区域ATP，葡萄糖和乳酸含量;和伞形酮荧光成像的组织pH值。没有动物表现出局灶性血流动力学或生化异常。在LDH阴性的SHR-SP中，整体CBF为1.1 +/- 0.3 mt g（-1）min-L，皮质CPS为10.1 +/- 3.1 mol，g（-1）min（-1），皮质ATP、葡萄糖、乳酸和pH水平均在正常范围内。在有功能性症状的SHR-SP中，ATP、葡萄糖和乳酸水平也正常，但组织pH显示室周水肿，CBF显著降低至0.7 +/- 0.2 mt g（-1）min（-1）（P < 0.001），皮质CPS显著降低至6.7 +/- 2.1 nmol g（-1）min（-1）（P < 0.001）。SHR-SP脑灌注量的下降与功能障碍的严重程度和蛋白质合成的下降显著相关。我们的观察结果表明，SHR-SP已经开发出明显的脑梗死的表现之前的功能症状和症状是由全球CBF和皮质CPS下降。SHR-SP中的遗传异常与弥漫性血管过程相关，该过程导致局灶性脑梗死发生前的血流全面失代偿。
Genomic screening of hybrids from stroke-prone (SHR-SP) and stroke-resistant spontaneously hypertensive rats (SHR) identified a STR1 locus on the rat chromosome 1, which correlates with the susceptibility to cerebral stroke but not with hypertension. The authors examined whether this genetic abnormality is associated with hemodynamic or metabolic alterations in the brain that can be detected before the manifestation of brain infarction. Starting at 6 weeks of age, SHR-SP were fed with a salt-rich diet to accelerate arterial hypertension. At the age of 12 weeks, animals developed functional symptoms and were age-matched with symptom-negative SHR-SP to differentiate between presymptomatic and postsymptomatic changes. Brains were investigated by multiparametric imaging comprising quantitative double-tracer autoradiography of CBF and cerebral protein synthesis (CPS); bioluminescence imaging of regional ATP, glucose, and lactate content; and umbellifer-one fluoroscopic imaging of tissue pH. None of the animals exhibited focal hemodynamic or biochemical abnormalities. Ln symptom-negative SHR-SP, global CBF was 1.1 +/- 0.3 mt g(-1) min-L, cortical CPS was 10.1 +/- 3.1 mol,g(-1) min(-1) and cortical ATP, glucose, lactate, and pH levels were in the normal range. In SHR-SP with functional symptoms, ATP, glucose, and lactate levels also were normal, but tissue pH exhibited periventricular alkalosis, CBF was significantly reduced to 0.7 +/- 0.2 mt g(-1) min(-1) (P < 0.001), and cortical CPS was significantly reduced to 6.7 +/- 2.1 nmol g(-1) min(-1) (P < 0.001). The decline in brain perfusion of SHR-SP correlated significantly with both the severity of functional deficits and the decline of protein synthesis. Our observations demonstrate that SHR-SP had already developed functional symptoms before the manifestation of overt brain infarcts and that the symptoms are initiated by a decline in global CBF and cortical CPS. Genetic abnormalities in SHR-SP are associated with a diffuse vascular process that results in global decompensation of blood flow well before the onset of focal brain infarction.