Prospective Study of Extracellular Vesicles in Plasma as Potential Biomarkers for Silent Brain Infarcts
Lincey Wilson1, Duaa Dakhlallah, PhD 2, Anna Zukowski, MS23, Jacob Ralston, MS13, Kate Karelina, PhD5, James Simpkins, PhD5, Muhammad Alvi4, Candace Brown, PhD5
1West Virginia Clinical and Translational Sciences Institute, West Virginia University, 2Department of Surgery, Department of Surgery, 3Department of Neuroscience, 4Department of Neurology, West Virginia University School of Medicine, 5Department of Neuroscience, West Virginia University School of Medicine / Rockefeller Neuroscience Institute
Objective:
This study will identify plasma-derived extracellular vesicle (EV) biomarkers to distinguish patients with
silent brain infarcts (SBIs) from controls and individuals with ischemic stroke.
Background:
SBIs are small areas of cortical or subcortical gliosis found incidentally on brain imaging without clinical deficits on examination. Individuals with SBIs are at increased risk for future strokes as well as more severe strokes. Characterizing the size, number, and content of plasma EVs may provide unique biomarkers to identify patients with SBIs.
Design/Methods:
This is an ongoing minimal-risk study approved by the Institutional Review Board (IRB) for 80 patients
recruited from the neurology inpatient service and separated into three groups: control, SBI and acute or chronic stroke. Controls are patients with a negative MRI. EVs were isolated from patient plasma via
sequential centrifugation followed by characterization of size and plasma concentration by Nanoparticle
Tracking Analysis (NTA) and assessment of EV charge for measuring Zetapotential (ZP).
Results:
Preliminary analysis of 15 subjects [control (n=5), SBI (n=6) and acute or chronic stroke (n=4)] showed a
significant increase in mean neutrophil to lymphocyte ratio (NLR) of SBI patients vs. controls (p=0.02)
and acute/chronic stroke vs. controls (p= 0.01). NTA analysis revealed a trending increase in the mean
size of EVs from SBI patients compared to controls (p=0.08). The ZP of EVs from SBI patients compared
to controls showed a trending increase (p=0.061), while the difference between SBI and acute/chronic
stroke patients was not significant (p=0.22). ZP results suggest that plasma EVs from SBI patients are
more likely to exhibit increased coagulation, which increases the risk of ischemic stroke.
Conclusions:
Preliminary results demonstrate that EVs from SBI patients display a similar physiological phenotype to
acute/chronic stroke patients compared to controls based on the quantification of EV size, quantity, and
ZP. Ongoing studies will identify EV miRNA content for additional SBI biomarkers.