CXCL12 levels correlate with reduced stroke severity and lower risk of hemorrhagic transformation in stroke patients.

Background and purpose: Stroke is a leading cause of mortality and acquired disability. Acute-phase interventions like intravenous thrombolysis and mechanical thrombectomy have improved stroke prognosis, yet limitations persist, warranting novel therapeutic targets in cerebroprotection. Neutrophils play a key role in the post-stroke immune response, where recent studies have shown both detrimental and cerebroprotective roles. CXCL12 has emerged as a cytokine influencing neutrophil phenotype and potentially stroke severity, yet its effect in the acute phase remains controversial. Methods: In this prospective cohort study, 134 patients with ischemic stroke within 6 h of onset or with a wake-up stroke were included. We recorded clinical data, plasma CXCL12 levels, and neutrophil phenotype at admission, 24 h and 3 months post-stroke. We assessed stroke severity using NIHSS scores, ASPECTS scores, infarct volume at 24-72 h and functional outcomes at 3 months. Correlations between CXCL12, clinical severity, radiological findings, and functional outcomes were analyzed with regression models. A predictive model was developed using backward stepwise regression. Results: Higher admission CXCL12 concentrations were associated with lower radiological severity (ASPECTS) and reduced infarct volume at 24 h. Lower CXCL12 at 24 h was linked to increased hemorrhagic transformation risk, while no significant link was found with 3-month functional prognosis. Additionally, a positive correlation was observed between CXCL12 levels and plasma NETs markers. No associations were found between CXCL12 levels and neutrophil aging phenotype by nuclear segmentation. Conclusions: Our findings suggest CXCL12 levels are associated with acute stroke severity and with a lower risk of hemorrhagic transformation, though not with long-term functional outcomes. Further research is needed to elucidate the role of CXCL12 in stroke pathophysiology and to determine its potential relevance as a biomarker or therapeutic target.