Introduction Mechanical thrombectomy (MT) and tissue plasminogen activator are ischemic stroke treatments that assist in restoring blood flow to the brain tissue, but do not guarantee good outcomes. Detection of cellular alterations systemically in extracellular vesicles (EVs) could be invaluable to theragnostic. EVs are nanoparticles released from cells that carrying stimuli specific cargo (e.g. lipids, proteins, and nucleic acids) from one cell to another. We hypothesize that the ratio of pro brain derived neurotrophic factor (proBDNF) to BDNF expression (proBDNF/BDNF) can be clinically relevant and used to predict stroke outcomes.
Methods Human ischemic stroke plasma, collected during MT, and cardiovascular disease (CVD) control plasma, collected during diagnostic angiograms, were unbanked from the ‘Blood And Clot Thrombectomy Registry And Collaboration’ (BACTRAC; NCT03153683). EVs were isolated (Exoquick) then measured (Zetaview-NTA) before quantification of proBDNF and BDNF.
Results Stroke subjects (n=29) were significantly older (67 vs. 56 years; p=0.03) than the controls (n=18), though there was no difference in the representation of sex (p>0.9), body mass (p=0.64), or the presence of hypertension (p=0.50). Baseline EV characteristics also showed no significant difference in size (124.1 nm vs. 125.6 nm; p=0.9) or concentration (1.88 X109 vs. 1.89 X109; p=0.9). Stroke subjects exhibited increased EV proBDNF/BDNF compared to the controls (10.56 ± 1.8 vs. 4.13 ± 0.78; p=0.0008). This was primarily driven by significantly higher EV BDNF in stroke patients compared to controls (59 pg/mg vs. 14 pg/mg; p=0.027) and a lower variation of EV proBDNF expression in stroke (211.8 ± 26.6 vs.175.8 ± 42.6 pg/mL) compared to controls. EV proBDNF/BDNF positively correlated longer infarct time (p=0.0946, r2= 0.12) and decreased cognition (i.e., Montreal Cognitive Assessment (MoCA), p=0.03, r2= 0.487).
Discussion These data suggest that EV proBDNF/BDNF levels can reflect vascular changes that lead to decreased cognition and should be explored further for translational applications.
Disclosures A. Trout: None. D. Britsch: None. W. Naberhaus: None. J. Turchan-Cholewo: None. C. McLouth: None. L. Whitnel-Smith: None. J. Frank: None. J. Roberts: None. P. Shivani: None. D. Dornboss III: None. J. Harp: None. K. Pennypacker: None. A. Stowe: None. J. Fraser: None.
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