Acute ischemic stroke and reperfusion drive molecular immune-vascular activations detectable in peripheral blood.

Abstract

Inflammation drives damage in acute ischemic stroke (AIS). Here, we map temporal and molecular mechanisms of immune-vascular response in patients with AIS treated with endovascular thrombectomy (EVT) for anterior circulation large-vessel occlusion. In this prospective cohort, 52 patients underwent serial peripheral blood sampling at groin puncture (Pre), catheter withdrawal (T0), and 6, 24, and 48 hours post-reperfusion. Thirteen immune and vascular players were quantified by mesoscale multiplex assays. Clinical outcomes were the modified Rankin Scale (mRS) score at 3 months and the National Institutes of Health Stroke Scale (NIHSS) at 24 hours. Adjusted by age, baseline Alberta Stroke Program Early CT Score (ASPECTS) and NIHSS scores, higher pre-EVT peripheral blood levels of interleukin (IL)-1β, IL-4, IL-10, and IL-13 were associated with poorer 24-hours NIHSS. Post-EVT reperfusion, IL-6 and its downstream effectors vascular cell adhesion molecule- (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) levels rose in peripheral blood over time, suggesting cerebrovascular inflammation, accompanied by the increased levels of acute-phase reactants C-reactive protein (CRP) and serum amyloid A (SAA), indicative of a systemic inflammatory engagement. In the same timeframe, interferon-gamma (IFN-γ) blood levels decreased. Adjusted by age, baseline ASPECT and NIHSS scores, and pre-thrombectomy biomarker levels, higher post-EVT levels of IL-6, VCAM-1, ICAM-1, and SAA were associated with poorer 24-hours NIHSS and unfavorable mRS 3 month outcomes, supporting an evolving immune dysregulation following AIS. This exploratory study points to immune and vascular activation mechanisms from pre- to post-EVT, representing possible disease indicators and targets.