Glucocorticoids combined with anticoagulation modulate the central NLRP3/NETosis inflammatory process in patients with severe cerebral venous thrombosis: a human mechanistic exploratory study.

OBJECTIVES: Neutrophil-mediated neuroinflammation plays a crucial role in secondary brain injury following severe cerebral venous thrombosis (CVT). Although previous studies have reported that the combination of glucocorticoids (GCs) and anticoagulation is associated with improved clinical outcomes, its mechanism remains unknown. We hypothesized that the combination therapy may exert benefit by modulating neutrophil-driven inflammation. METHODS: This study included a cohort of 50 patients diagnosed with severe CVT who were undergoing treatment with the combination therapy. We investigated the dynamic alterations in the NLRP3/NETosis inflammatory process by analyzing paired serum and cerebrospinal fluid (CSF) samples collected at baseline and 1 week post-treatment. Neurological function was systematically evaluated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). RESULTS: The combined therapy was associated with reduced CSF levels of key NLRP3/NETosis mediators, including NOD-like receptor family pyrin domain containing 3 (NLRP3), polymorphonuclear neutrophil elastase (PMN Elastase), myeloperoxidase (MPO), and citrullinated histone H3 (CitH3), while the corresponding serum levels were unchanged. Baseline CSF levels of NLRP3, PMN Elastase, and MPO strongly correlated with admission NIHSS and mRS. Early reductions in these central markers were associated with neurological improvement at discharge (ΔNIHSS). Moreover, patients with unfavorable outcomes (discharge mRS > 1) had significantly higher baseline NIHSS and CSF NLRP3 levels. CONCLUSIONS: The combined therapy may alleviate severe CVT by modulating the central NLRP3/NETosis inflammatory process.