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.