Brain-derived extracellular vesicles as serologic markers of brain injury following cardiac arrest: A pilot feasibility study

Aim Assessment of neurologic injury within the immediate hours following out-of-hospital cardiac arrest (OHCA) resuscitation remains a major clinical challenge. Extracellular vesicles (EVs), small bodies derived from cytosolic contents during injury, may provide the opportunity for “liquid biopsy” within hours following resuscitation, as they contain proteins and RNA linked to cell type of origin. We evaluated whether micro-RNA (miRNA) from serologic EVs were associated with post-arrest neurologic outcome. Methods We obtained serial blood samples in an OHCA cohort. Using novel microfluidic techniques to isolate EVs based on EV surface marker GluR2 (present on excitatory neuronal dendrites enriched in hippocampal tissue), we employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) methods to measure a panel of miRNAs and tested association with dichotomized modified Rankin Score (mRS) at discharge. Results EVs were assessed in 27 post-arrest patients between 7/3/2019 and 7/21/2022; 9 patients experienced good outcomes. Several miRNA species including miR-124 were statistically associated with mRS at discharge when measured within 6 hours of resuscitation (AUC = 0.84 for miR-124, p < 0.05). In a Kendall ranked correlation analysis, miRNA associations with outcome were not strongly correlated with standard serologic marker measurements, or amongst themselves, suggesting that miRNA provide distinct information from common protein biomarkers. Conclusions This study explores the associations between miRNAs from neuron-derived EVs (NDEs) and circulating protein biomarkers within 6 hours with neurologic outcome, suggesting a panel of very early biomarker may be useful during clinical care. Future work will be required to test larger cohorts with a broader panel of miRNA species.