Ischemic Stroke and Intracerebral Hemorrhage Genomic Studies in Humans

人类缺血性中风和脑出血基因组研究

• 批准号: 7361350
• 负责人: FRANK R SHARP
• 金额: $ 57.19万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7361350
• 关键词: Acute; Address; Age; Animals; Blood; Brain; Brain imaging; Cerebral hemisphere hemorrhage; Chronic; Clinical; Data; Development; Diagnosis; Etiology; Future; Gender; Gene Expression; Genes; Genomics; Hemorrhage; Hereditary Disease; Hour; Human; Hypoglycemia; Image; Injury; Ischemic Stroke; Leukocytes; Magnetic Resonance Imaging; Migraine; Molecular Profiling; Outcome; Pathogenesis; Pathology; Patients; Pharmaceutical Preparations; Race; Recording of previous events; Research Personnel; Research Priority; Reverse Transcriptase Polymerase Chain Reaction; Role; Sensitivity and Specificity; Status Epilepticus; Stroke; Time; Tissues; United States National Institutes of Health; Whole Blood; base; cohort; day; monocyte; outcome forecast; peripheral blood; programs; response; stroke therapy; therapy development

DESCRIPTION: Ischemic stroke is currently diagnosed using the clinical presentation combined with brain imaging. Brain imaging also helps differentiate ischemic stroke from intracerebral hemorrhage. Though imaging is excellent for diagnosing stroke, it would be desirable if stroke therapies could be given at early times without brain imaging. Thus the Stroke PRG determined that the development of stroke blood markers is among the top NINDS stroke research priorities. To address this, our group first demonstrated that ischemic stroke, intracerebral hemorrhage, status epilepticus and hypoglycemia produced unique gene expression profiles in blood of experimental animals. We confirmed this in human patients with stroke that show changes of gene expression in whole blood at 3, 5 and 24 hours after ischemic stroke, with the changes of expression of 18 genes predicting 14 of 15 patients with stroke at 5 hours and 15 of 15 patients with stroke at 24 hours. The data strongly supports the studies in the present proposal that will show different blood genomic profiles in patients with ischemic strokes as compared to patients with intracerebral hemorrhage and as compared to controls. There are two aims in this study. Aim #1a: Describe the whole blood genomic profiles of patients with ischemic strokes at 3, 24 and 72 hours as compared to age, gender and race-matched control patients without strokes. Aim#1b: Confirm that the genes most regulated on microarrays following ischemic stroke are similarly regulated using quantitative RT-PCR, and that these genes predict a second cohort of ischemic stroke patients compared to controls. Aim #2a: Describe the whole blood genomic profiles of patients with intracerebral hemorrhages at 3 to 72 hours after the hemorrhages, and compare to the profiles of control patients and to patients with ischemic strokes. Aim #2b: Confirm that the genes regulated following intracerebral hemorrhage on microarrays are similarly regulated using RT-PCR, and that these genes predict a second cohort of intracerebral hemorrhage patients compared to ischemic stroke patients and compared to controls. Hypotheses: The blood genomic profiles of patients with intracerebral hemorrhages will differ from patients with ischemic strokes and from control patients. The genomic responses of white blood cells will be useful for diagnosis, and will increase understanding of the etiology, pathogenesis and prognosis of ischemic stroke and intracerebral hemorrhage, and potentially guide acute and chronic treatment in the future.

描述：缺血性脑卒中目前是通过临床表现结合脑成像来诊断的。脑成像也有助于区分缺血性中风和脑出血。虽然脑成像在诊断中风方面非常出色，但如果能在早期不进行脑成像的情况下进行中风治疗，那将是可取的。因此，卒中PRG确定卒中血液标志物的开发是NINDS卒中研究的首要任务之一。为了解决这个问题，我们的团队首先证明了缺血性中风、脑出血、癫痫持续状态和低血糖在实验动物的血液中产生了独特的基因表达谱。我们在人类中风患者中证实了这一点，缺血性中风后3、5和24小时全血中基因表达的变化，18个基因的表达变化预测了15例中风患者中5小时的14例和15例中风患者中24小时的15例。这些数据有力地支持了本提案中的研究，这些研究将显示缺血性中风患者与脑出血患者以及与对照组相比的不同血液基因组图谱。这项研究有两个目的。目的#1a：描述缺血性卒中患者在3、24和72小时的全血基因组图谱，与年龄、性别和种族匹配的对照组无卒中患者进行比较。目的#1b：利用定量RT-PCR证实在缺血性卒中后微阵列上最受调控的基因也受到类似的调控，并且与对照组相比，这些基因可以预测第二组缺血性卒中患者。目的#2a：描述脑出血患者在出血后3至72小时的全血基因组图谱，并与对照患者和缺血性中风患者的图谱进行比较。目的#2b：确认微阵列上脑出血后调节的基因与RT-PCR的调节相似，并且这些基因预测了脑出血患者与缺血性中风患者和对照组的第二队列。假设：脑出血患者的血液基因组图谱将不同于缺血性中风患者和对照患者。白细胞的基因组反应将有助于诊断，并将增加对缺血性脑卒中和脑出血的病因、发病机制和预后的了解，并有可能指导未来的急慢性治疗。