Cerebrospinal Fluid Markers Of Aging And Brain Disease

(1)阿尔茨海默病(AD)与脑神经元螺旋细丝中过度磷酸化的tau蛋白积聚有关。建立了检测脑脊液(CSF)中苏氨酸231磷酸化的tau蛋白浓度的免疫酶联免疫测定法。通过检测脑脊液中磷酸化tau，可以准确诊断AD，并跟踪AD的进程，具有较高的特异性和选择性。(2)将培养的PC12细胞置于0.1~100微摩尔的三氯化铝中孵育6h。Northern印迹分析显示，仅1微摩尔铝暴露后，线粒体电子传递链中的一种酶--细胞色素c氧化酶的一个亚单位的mRNA水平降低了70%。在AD和透析性痴呆患者的尸检脑中发现了这种低浓度，这表明铝在这些疾病中扮演了有毒的角色。(3)颈动脉内注入高渗糖溶液渗透性开放血脑屏障用于临床治疗恶性脑肿瘤，并在动物模型中允许药物和蛋白质进入脑内。开放涉及血管内皮细胞之间紧密连接的扩大。开放是通过细胞内钙离子的增加和内皮细胞骨架的收缩来调节的。用Na+/Ca~(2+)交换阻滞剂预处理的大鼠开放时间延长。

(1) Alzheimer disease (AD) is associated with accumulation of hyperphosphorylated tau protein within paired helical filaments of brain neurons. An immunologic ELISA assay was developed to measure the cerebrospinal fluid (CSF) concentration of tau protein phosphorylated at threonine 231. AD could be accurately diagnosed and its course followed with high specificity and selectivity by measuring phosphorylated tau in CSF. (2) Cultured PC12 cells were exposed to 0.1-100 micromole aluminum chloride for 6 hours. Northern blot analyses showed that the mRNA level of a subunit of cytochrome c oxidase, an enzyme in the mitochondrial electron transport chain, was reduced by 70% after exposure to only 1 micromole aluminum. This low concentration is found in postmortem brain from patients with AD and dialysis dementia, suggesting a toxic role for aluminum in these disorders. (3) Osmotic opening of the blood-brain barrier by intracarotid infusion of a hypertonic sugar solution is used clinically to treat malignant brain tumors and to grant access to brain of drugs and proteins in animal models. Opening involves the widening of tight junctions between vascular endothelial cells. Opening is mediated by increased intracellular Ca2+ and contraction of the endothelial cytoskeleton. Opening is prolonged in rats pretreated with a Na+/Ca2+ exchange blocker.