Plasma Profiles of Neuroglial Injury Biomarkers after Ischemic Stroke

Objective To determine the temporal profiles of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (t-tau), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in plasma the first week after acute ischemic stroke, and identify the optimal time points for assessing infarct volume by these biomarkers. Patients & Methods In this cohort study, biomarker plasma concentrations were determined daily over the first week and at 90 days after symptom onset in patients with acute ischemic stroke. A brain MRI was performed on day three. Temporal variations in biomarker levels were analyzed using linear mixed-effects models, and optimal time points for infarct volume correlation were identified with continuous Pearson analysis. Results 38 patients with a median age of 78 (IQR 72–86) and mean infarct volume of 5.5 (IQR 1.6–17) cm 3 were included. We identified three distinct temporal patterns: (1) a parabolic trajectory of GFAP, reaching zenith after three days, (2) a consistent increase in NFL throughout the week, and (3) an initial surge in t-tau and UCHL1 levels, stabilizing by day three. The optimal time point for infarct volume correlation occurred at 119 h for GFAP (r = 0.94, 95% CI: [0.84–0.98]), 144 h for NFL (r = 0.78, [0.47, 0.92]), 122 h for t-tau (r = 0.82, [0.56, 0.93]) and 113 h for UCHL1 (r = 0.83, [0.60, 0.93]). Interpretation This high-resolution serial sampling of plasma GFAP, NFL, t-tau, and UCHL1 the first week after acute ischemic stroke identified three distinct temporal profiles. These biomarkers provided the most accurate infarct volume assessment 4–6 days after symptom onset. Clinicaltrials.gov NCT03812666 (registration date 2019-01-23).