Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident.

Autor: Fringuello A; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.; Department of Neurology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA., Tatman PD; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.; Medical Scientist Training Program, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.; Department of Pharmacology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA., Wroblewski T; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.; Department of Neurology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA., Thompson JA; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.; Department of Neurology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA., Yu X; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA., Lillehei KO; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA., Kowalski RG; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.; Department of Neurology, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA., Graner MW; Department of Neurosurgery, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Jul 22; Vol. 22 (15). Date of Electronic Publication: 2021 Jul 22.
DOI: 10.3390/ijms22157847
Abstrakt: 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.
Databáze: MEDLINE
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