Plasma Profiles of Neuroglial Injury Biomarkers after Ischemic Stroke

Transl Stroke Res. 2025 Dec;16(6):2185-2194. doi: 10.1007/s12975-025-01380-y. Epub 2025 Sep 3.

Abstract

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) cm3 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).

Keywords: Glial fibrillary acidic protein; Neurofilament; Stroke; Tau; Ubiquitin carboxy-terminal hydrolase L1.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Brain Ischemia* / blood
  • Cohort Studies
  • Female
  • Glial Fibrillary Acidic Protein* / blood
  • Humans
  • Ischemic Stroke* / blood
  • Ischemic Stroke* / diagnostic imaging
  • Magnetic Resonance Imaging
  • Male
  • Neurofilament Proteins* / blood
  • Neuroglia* / metabolism
  • Neuroglia* / pathology
  • Ubiquitin Thiolesterase* / blood
  • tau Proteins* / blood

Substances

  • Biomarkers
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • neurofilament protein L
  • Neurofilament Proteins
  • tau Proteins
  • Ubiquitin Thiolesterase
  • UCHL1 protein, human

Associated data

  • ClinicalTrials.gov/NCT03812666