Association of Serum Biomarkers with Post-Thrombolytic Early Neurological Improvement in Stroke: A Comprehensive Protein Microarray Analysis From INTRECIS Study

Objective Early neurological improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue in a prospective cohort. Methods In INTRECIS study, five centers were designed to consecutively collect the blood sample from enrolled patients. Enrolled patients with ENI and without ENI were matched by propensity score matching with the ratio of 1:1. Preset 49 biomarkers were measured by protein microarray analysis. Enrichment of Gene Ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. Results Of 358 patients, 19 occurred ENI, who were assigned as ENI group, while 19 matched patients without ENI were assigned as Non ENI group. A total of 9 biomarkers were found different, among which 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 ENI group, compared with those in Non ENI group. Interpretation: Our finding indicated that pretreatment serum CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α levels were associated with post-thrombolytic ENI in ischemic stroke. The role of these biomarkers warrant further investigation. Registration-URL : https://www.clinicaltrials.gov; Unique identifier: NCT02854592.