1. ¹MIND Institute and Departments of Neurology, University of California at Davis, Sacramento, California, USA
2. ²MIND Institute and Departments of Pathology, University of California at Davis, Sacramento, California, USA
3. ³Departments of Neurology, University of Cincinnati, Cincinnati, Ohio, USA
4. ⁴Departments of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio, USA
5. ⁵MIND Institute and Departments of Neurological Surgery, University of California at Davis, Sacramento, California, USA

Correspondence: Dr FR Sharp, MIND Institute and Department of Neurology, University of California at Davis, 2805 50th Street – Room 2416, Sacramento, CA 95817, USA. E-mail: frank.sharp@ucdmc.ucdavis.edu

Received 10 September 2005; Revised 11 October 2005; Accepted 7 November 2005; Published online 4 January 2006.

Abstract

Ischemic brain and peripheral white blood cells release cytokines, chemokines and other molecules that activate the peripheral white blood cells after stroke. To assess gene expression in these peripheral white blood cells, whole blood was examined using oligonucleotide microarrays in 15 patients at 2.40.5, 5 and 24 h after onset of ischemic stroke and compared with control blood samples. The 2.4-h blood samples were drawn before patients were treated either with tissue-type plasminogen activator (tPA) alone or with tPA plus Eptifibatide (the Combination approach to Lysis utilizing Eptifibatide And Recombinant tPA trial). Most genes induced in whole blood at 2 to 3 h were also induced at 5 and 24 h. Separate studies showed that the genes induced at 2 to 24 h after stroke were expressed mainly by polymorphonuclear leukocytes and to a lesser degree by monocytes. These genes included: matrix metalloproteinase 9; S100 calcium-binding proteins P, A12 and A9; coagulation factor V; arginase I; carbonic anhydrase IV; lymphocyte antigen 96 (cluster of differentiation (CD)96); monocarboxylic acid transporter (6); ets-2 (erythroblastosis virus E26 oncogene homolog 2); homeobox gene Hox 1.11; cytoskeleton-associated protein 4; N-formylpeptide receptor; ribonuclease-2; N-acetylneuraminate pyruvate lyase; BCL6; glycogen phosphorylase. The fold change of these genes varied from 1.6 to 6.8 and these 18 genes correctly classified 10/15 patients at 2.4 h, 13/15 patients at 5 h and 15/15 patients at 24 h after stroke. These data provide insights into the inflammatory responses after stroke in humans, and should be helpful in diagnosis, understanding etiology and pathogenesis, and guiding acute treatment and development of new treatments for stroke.