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Article

Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident

1
Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
2
Department of Neurology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
3
Medical Scientist Training Program, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
4
Department of Pharmacology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
Currently: State University of New York Downstate Health Sciences University, Brooklyn, NY 11203, USA.
Academic Editor: Anuska V. Andjelkovic
Int. J. Mol. Sci. 2021, 22(15), 7847; https://doi.org/10.3390/ijms22157847
Received: 3 June 2021 / Revised: 18 July 2021 / Accepted: 20 July 2021 / Published: 22 July 2021
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Background: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines—many associated with worse outcomes—occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood–brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. Methods: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). Results: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. Conclusions: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery. View Full-Text
Keywords: extracellular vesicles; hemorrhagic stroke; inflammation; Glasgow Outcome Scale; Glasgow Coma Scale-Extended; cytokines; chemotaxis extracellular vesicles; hemorrhagic stroke; inflammation; Glasgow Outcome Scale; Glasgow Coma Scale-Extended; cytokines; chemotaxis
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MDPI and ACS Style

Fringuello, A.; Tatman, P.D.; Wroblewski, T.; Thompson, J.A.; Yu, X.; Lillehei, K.O.; Kowalski, R.G.; Graner, M.W. Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident. Int. J. Mol. Sci. 2021, 22, 7847. https://doi.org/10.3390/ijms22157847

AMA Style

Fringuello A, Tatman PD, Wroblewski T, Thompson JA, Yu X, Lillehei KO, Kowalski RG, Graner MW. Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident. International Journal of Molecular Sciences. 2021; 22(15):7847. https://doi.org/10.3390/ijms22157847

Chicago/Turabian Style

Fringuello, Anthony, Philip D. Tatman, Tadeusz Wroblewski, John A. Thompson, Xiaoli Yu, Kevin O. Lillehei, Robert G. Kowalski, and Michael W. Graner. 2021. "Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident" International Journal of Molecular Sciences 22, no. 15: 7847. https://doi.org/10.3390/ijms22157847

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