Increased interleukin-6 levels in neuron-derived plasma small extracellular vesicles in patients with aneurysmal subarachnoid hemorrhage

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke characterized by high rates of mortality and disability. Identifying circulating biomarkers is helpful to improve prognosis. In this study, for the first time, we identify circulating interleukin-6 (IL-6) levels in neuron-derived small extracellular vesicles (NDSEVs) as potential biomarkers in prognosis of aSAH.Methods We extracted small extracellular vesicles from the plasma of aSAH patients and healthy controls and enriched them using sequential precipitation and anti-L1CAM antibody immunoabsorption. Subsequently, we determined IL-6 levels using an enzyme-linked immunosorbent assay (ELISA).Results Plasma IL-6 NDSEVs showed distinct pattern differences between aSAH patients and healthy controls. There were significant correlations of IL-6concentrations in plasma with severity in aSAH. The AUCs of IL-6 for distinguishing the severe aSAH patients from mild aSAH patients were 0.961. After multivariate logistic regression analysis, only age, acute hydrocephalus,and the levels of IL-6 NDSEVs enabled prediction of neurological outcome at 1 year. The IL-6 NDSEVs levels were greater and positively associated with disease and prognosis of aSAH patients.Conclusions These data suggest a neuroinflammatory cascade in aSAH patients. IL-6 NDSEVs may be a biomarkers to monitor the progression of aSAH.