Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans.

Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans.
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DOI:
10.1038/jcbfm.2011.45
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发表时间:
2011-07
期刊:
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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全基因组表达微阵列可用于研究血液中的基因表达,其部分来自白细胞、未成熟血小板和红细胞。由于这些细胞在中风的发病机制中很重要,RNA提供了这些细胞对中风反应的指标。我们在大鼠中的研究已经显示了在缺血性中风、出血、癫痫持续状态、缺氧、低血糖、全脑缺血和模拟人类短暂性脑缺血发作的短暂局灶性缺血后24小时的特异性基因表达变化。人类研究显示缺血性中风后基因表达发生变化。这些基因谱预测具有>90%灵敏度和特异性的第二群组。由大血管动脉粥样硬化和心源性栓塞引起的缺血性卒中的基因谱已被描述为预测第二队列的敏感性和特异性>85%。动脉粥样硬化基因与凝血、血小板和单核细胞相关,心源性栓塞基因与炎症、感染和中性粒细胞相关。这些基因图谱预测了58%的隐源性患者的中风原因。这些研究将提供诊断、预后和治疗标志物,并将促进我们对人类中风的理解。测量所有编码和非编码RNA沿着选择性剪接转录本的新技术将显著推进人类卒中的分子研究。
Whole genome expression microarrays can be used to study gene expression in blood, which comes in part from leukocytes, immature platelets, and red blood cells. Since these cells are important in the pathogenesis of stroke, RNA provides an index of these cellular responses to stroke. Our studies in rats have shown specific gene expression changes 24 hours after ischemic stroke, hemorrhage, status epilepticus, hypoxia, hypoglycemia, global ischemia, and following brief focal ischemia that simulated transient ischemic attacks in humans. Human studies show gene expression changes following ischemic stroke. These gene profiles predict a second cohort with >90% sensitivity and specificity. Gene profiles for ischemic stroke caused by large-vessel atherosclerosis and cardioembolism have been described that predict a second cohort with >85% sensitivity and specificity. Atherosclerotic genes were associated with clotting, platelets, and monocytes, and cardioembolic genes were associated with inflammation, infection, and neutrophils. These gene profiles predicted the cause of stroke in 58% of cryptogenic patients. These studies will provide diagnostic, prognostic, and therapeutic markers, and will advance our understanding of stroke in humans. New techniques to measure all coding and noncoding RNAs along with alternatively spliced transcripts will markedly advance molecular studies of human stroke.
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