Temporal Dynamics of Circulating Syndecan-1 in Acute Ischemic Stroke and Their Association with Recanalization...

and Purpose: The endothelial glycocalyx (EG) is a protective carbohydrate-rich layer lining the luminal surface of endothelial cells and a key component of the neurovascular unit, where it contributes to blood-brain barrier (BBB) integrity, vascular permeability control, and regulation of inflammatory and hemostatic responses. Disruption of the EG is increasingly recognized as an early marker of endothelial injury in acute vascular diseases. Syndecan-1, released during glycocalyx degradation, is a potential biomarker of endothelial dysfunction and may reflect vascular injury in acute ischemic stroke, although its temporal dynamics and clinical implications remain poorly understood.

In this prospective observational cohort study, adults with first-ever AIS presenting within 12 hours of symptom onset were enrolled at a tertiary stroke center. Serum syndecan-1 concentrations were measured at admission, 24 hours, and 48 hours after stroke onset and compared with controls. Associations between syndecan-1 concentrations, clinical and imaging characteristics, recanalization therapy, and 90-day functional outcomes were analyzed.

Fifty-six patients with AIS and 73 controls were included. Compared with controls, syndecan-1 concentrations did not differ significantly at baseline (p=0.658) but were significantly higher at 24 and 48 hours (both p<0.001). In the linear mixed-effects model, there was an overall effect of time (p=0.032), with a significant increase at 24 hours relative to baseline (p=0.008), but not at 48 hours (p=0.135). Lower 48-hour syndecan-1 concentrations were associated with unfavorable 90-day functional outcome in the unadjusted analysis (p=0.005), although this association was not independently maintained in the overall multivariable model (p=0.064). Exploratory descriptive analyses showed different numerical patterns according to recanalization therapy, but no formal between-group longitudinal difference was established. Among patients receiving recanalization therapy, syndecan-1 concentration at 48 hours was inversely associated with unfavorable 90-day outcome in an exploratory multivariable analysis (OR 0.94, 95% CI 0.90-0.99; p=0.03).

Circulating syndecan-1 concentrations vary during the acute phase of AIS. Concentrations were significantly higher than those of controls at 24 and 48 hours, whereas the within-patient increase relative to baseline was statistically significant only at 24 hours. The data do not establish different temporal trajectories according to recanalization therapy, and the subgroup prognostic finding should be considered hypothesis-generating. These findings do not directly demonstrate cerebral glycocalyx degradation or blood-brain barrier injury but support further investigation of syndecan-1 as a time-dependent circulating marker in AIS.