Cerebrovascular Extracellular Vesicles are Increased in Acute- and Chronic-Cerebrovascular Events and Associate with Cognitive Impairment
Cameron Owens1, Camila Bonin Pinto1, Eva Troyano Rodriguez1, Zsofia Szarvas1, Laura Boada-Robayo2, Demian Rudyk1, Stefano Tarantini1, Calin Prodan2, Andriy Yabluchanskiy1, Faddi Saleh Velez2
1Neurosurgery, 2Neurology, University of Oklahoma Health Sciences Center
Objective:
Determine plasma concentration of cerebrovascular endothelial extracellular vesicles (CEEVs) between controls (CN) and patients with acute- and chronic-cerebrovascular events. Secondarily, we evaluated cognitive performance in our sample to assess the relationship of CEEVs and cognition.
Background:
Endothelial extracellular vesicles (EEVs) are known to amplify during insult and carry cargo that can have deleterious effects on target cells. We previously showed that increased CEEVs significantly associated with impaired cognitive performance and subclinical load of small vessel ischemic lesions. However, it is unknown whether CEEVs are elevated in acute- and chronic-cerebrovascular events.
Design/Methods:
CEEV concentration and ratio (CEEVs/systemic EEVs) were conducted by nano-flow cytometry and cognition was assessed by Montreal Cognitive Assessment (MoCA). Controls with no history of stroke or cognitive impairment (CN: n=8, 68.9 ±5.8 years old (y/o), 50% females), patients with chronic cerebrovascular events (CCE) of any etiology, hemorrhagic or ischemic (n=4) or history of transient ischemic attack (n=2) >1 month (CCE: 70.5 ±9.3 y/o, 50% females) and acute cerebrovascular events (ACE) of any etiology, hemorrhagic or ischemic (ACE: n=5, 47.4 ±10.0 y/o, 60% females) were included in data analysis. MoCA was conducted in all CN (27.6 ±1.1) and CCE patients (19.5 ±4.9) and two ACE patients (25.1 ±5.0).
Results:
Kruskal-Wallis’s test with Dunn’s correction showed increased ratio of CEEVs in CCE (median=12%, IQR=[7.5-30.12], p=0.04) and ACE (median=20.38%, IQR=[11.5-35.1], p=0.02) compared to CN (median=3.4%, IQR=[2.5-7.1) with no difference between CCE and ACE. Spearman correlation determined a moderate negative relationship with a trend towards significance between CEEV ratio and cognition (n=16, r=-0.46, p=0.08).
Conclusions:
These data support our previous findings of CEEVs as markers of cognitive impairment and expand the association between CEEVs and subclinical small vessel lesions to acute- and chronic-cerebrovascular events. Determining the mechanistic underpinning for continued CEEV potentiation from acute- to chronic-stroke may provide a therapeutic route for mitigating post-stroke cognitive impairment.
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