Circulating Aquaporin-4 as A biomarker of early neurological improvement in stroke patients: A pilot study

Abstract

Patients’ outcome prediction after ischemic stroke is still challenging. Aquaporin-4 (AQP4) is a water channel that is up-regulated in the brain after the ischemic event, but its presence in bloodstream of stroke patients has not been previously studied. The aim of this pilot study was to investigate circulating AQP4 levels after stroke and its correlation with infarct growth and neurological outcome.AQP4 level was determined by ELISA in serum from 42 t-PA-treated ischemic stroke patients at admission (before t-PA) and 13 healthy subjects. To assess infarct growth, serial brain diffusion-weighted magnetic resonance images were performed at hospital admission and 1–3 days after. Neurological improvement was defined as a ≥4-point decrease in NIHSS score compared to baseline score.Despite stroke patients and healthy controls had similar baseline circulating AQP4 levels, among strokes AQP4 level negatively correlated with NIHSS score at admission (R= −0.34, p = 0.029) and with infarct growth after 1–3 days of stroke onset (R=−0.36; p = 0.018). Furthermore, baseline AQP4 level was higher in those stroke patients showing a neurological improvement 48 h after stroke onset (p = 0.030) and at hospital discharge (p = 0.037). Baseline AQP4 levels also resulted to be an independent predictor of good neurological outcome at both studied time points (ORadj: 14.33[1.82–112.92], p = 0.012 at 48 h; ORadj: 4.86[0.98–24.12], p = 0.053 at discharge) in logistic regression analysis, adjusted by age, sex, baseline NIHSS and significant variables in the univariate analysis.Overall, we have explored circulating AQP4 levels, and our data suggest that AQP4 could be used as a biomarker of neurological recovery in the acute-subacute phase of ischemic stroke.