Association of serum biomarkers with early neurologic improvement after intravenous thrombolysis in ischemic stroke

PLoS One. 2022 Oct 31;17(10):e0277020. doi: 10.1371/journal.pone.0277020. eCollection 2022.

Abstract

Background: Early neurologic improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue based on a prospective cohort.

Methods: In INTRECIS study, five centers were designed to consecutively collect blood sample from enrolled patients. The patients with ENI and without ENI were matched by propensity score matching with a ratio of 1:1. Preset 49 biomarkers were measured through microarray analysis. Enrichment of gene ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers.

Results: Of 358 patients, 19 patients with ENI were assigned to ENI group, while 19 matched patients without ENI were assigned to Non ENI group. A total of nine biomarkers were found different between two groups, in which serum levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in the ENI group, compared with those in the Non ENI group.

Conclusions: We found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in stroke. The role of biomarkers warrants further investigation.

Trial registration: Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT02854592.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Brain Ischemia* / drug therapy
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Ischemic Stroke*
  • Ligands
  • Prospective Studies
  • Stroke* / drug therapy
  • Thrombolytic Therapy
  • Tissue Plasminogen Activator / therapeutic use
  • Treatment Outcome

Substances

  • Biomarkers
  • Fibrinolytic Agents
  • Ligands
  • Tissue Plasminogen Activator

Associated data

  • ClinicalTrials.gov/NCT02854592

Grants and funding

The study was funded by grants from National Key R&D Program of China (2017YFC1308203), and the Project on Research and Application of Effective Intervention Techniques for Chinese Stroke Guidelines from the National Health and Family Planning Commission in China (GN-2016R0008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.