Technology overview: RNA and mechanisms of stroke relevant to ISCDX

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The Ischemia Care platform of testing and services is built upon genes that relate to known RNA pathways that differentially express based upon cause of ischemic stroke.

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Stroke is a disease of vasculature and blood

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Ischemic stroke, in most cases, is a disease of the vasculature and blood, involving platelets, red blood cells, clotting factors, inflammatory cells, and endothelium. Though the result is ischemic brain damage, the primary disease process does not generally relate to the brain tissue itself except in some diseases such as mitochondrial diseases. Most strokes in humans are due to large vessel atherosclerotic disease, cardioembolic disease (blood clots), and lacunar small vessel disease. Atherosclerosis is an inflammatory disease due to a complex interaction between lipids, endothelium, and vascular risk factors  .  Atherosclerotic plaques cause stroke by thromboembolism of clot/platelets formed at the plaque or following plaque fragmentation   . Cardioembolic stroke represents a group of cardiac disorders with a propensity to form blood clots in the heart that embolize to brain   . The third major stroke subtype, lacunar, is due to ‘lipohyalinosis’ of small penetrating vessels in the brain   .

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Why leukocyte RNA is meaningful in blood of stroke patients

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Leukocytes (neutrophils, lymphocytes, monocytes), platelets, red blood cells, and other cells interact with each other and with endothelial cells in normal vessels.  Leukocyte interactions with endothelial cells, platelets, atherosclerotic plaque, blood clots, and intravascular molecules (cytokines, chemokines, hormones, others) likely account for some changes of gene expression following stroke.  Leukocytes also signal to these other cell types, which also account for changes of gene expression. In simple terms, Leukocytes interact with cell types relevant to ischemic stroke.

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1. Biomarkers of Acute Stroke Etiology (BASE) Study Methodology, Jauch, E.C., Barreto, A.D., Broderick, J.P. et al. Transl. Stroke Res. (2017) 8: 424. https://doi.org/10.1007/s12975-017-0537-3

2. Chalela, 2009; Chamorro and Hallenbeck, 2006; Hansson, 2009

3. Chalela, 2009; Wu and Grotta, 2010

4. Babarro et al, 2009

5. Nahet al, 2010; Stevenson et al, 2010