BLOOD MARKERS OF ACUTE ISCHEMIC STROKE

University Of Cincinnati, Cincinnati OH

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Abstract

The diagnosis of cute stroke is based upon clinical findings and brain imaging. Blood markers of acute ischemic stroke or tPA-induced hemorrhage would be useful for initiating early treatment with tPA (tissue plasminogen activator) and related agents. This proposal will examine white blood cell RNA expression following ischemic compared to hemorrhagic stroke because microarray technology can survey thousands of RNAs at one time and because transcriptional responses can be rapid. Moreover, preliminary data in rodents shows a unique genomic response of white blood cells one day following ischemic stroke and hemorrhagic stroke when compared to each other and when compared to controls. This proposal will demonstrate the blood genomic changes at 24h following ischemic strokes and intracerebral hemorrhages in patients that do or do not receive tPA. The first aim will use human oligonucleotide arrays to examine the white blood cell genomic response at 24h after ischemic stroke, 24h after intracerebral hemorrhages, and in age, race and sex-matched control patients without neurological disease. We will show that there is a specific blood genomic profile that correlates with ischemic strokes compared to intracerebral hemorrhage and control patients; and that there is a blood genomic profile that correlates with intracerebral hemorrhages as compared to control and ischemic stroke patients. The second aim will use olgionucleo9tide microarrays to examine the blood genomic response at 24H in ischemic stroke patients that receive tPA+ eptifibatide by 3 hours. The blood genomic expression patterns in patients with tPA associated hemorrhages will be compared to those without hemorrhages as assessed by CT/MRI. One of the long-term goals as to identify, among the genes induced at 24h following an ischemic stroke in order to be able to diagnose ischemic cerebral events between 2 and 24h after the stroke using a blood test. Another long-term goal is to identify a set of genes in peripheral white blood cells at 2h after stroke that would be associated with tPA-associated intracerebral hemorrhages that might help guide the dose or decision to give thrombolytics.