Ischemic Stroke and Intracerebral Hemorrhage Genomic Studies in Humans

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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.