Association of decreased serum Netrin-1 with inflammatory markers, neurological severity, and 3-month outcome in hypertensive intracerebral hemorrhage

Objective To compare serum Netrin-1 levels among hypertensive intracerebral hemorrhage (HICH) patients, hypertensive patients without cerebrovascular lesions and healthy controls, and analyze its correlations with inflammatory markers, neurological deficit severity and 3-month functional prognosis.Methods This single-center retrospective cohort enrolled 294 participants from September 2021 to September 2022, including 98 HICH patients, 92 uncomplicated primary hypertension patients and 104 healthy subjects. Serum samples were collected within routine clinical time windows, yet the intervals from hemorrhage onset and acute treatments to blood collection were inconsistent. Multiple subgroup, correlation and prognostic analyses were conducted with exact p-values presented; p < 0.01 was set as a strict threshold for primary interpretations.Results HICH patients had markedly lower serum Netrin-1 than healthy controls (p < 0.001), with no significant difference versus hypertensive patients (p = 0.083). Netrin-1 was negatively correlated with NIHSS, mRS, IL-6 and CRP, and positively correlated with IL-10. Its concentrations declined progressively with aggravated neurological impairment. Multivariate regression identified low Netrin-1, high NIHSS and brainstem hemorrhage as independent predictors of poor 3-month outcome (GOS 1–3). The internal ROC analysis showed an AUC of 0.896 (95%CI 0.817–0.923).Conclusion Reduced serum Netrin-1 correlates with severe neurological damage and unfavorable 3-month prognosis in HICH, serving as an independent prognostic indicator after covariate adjustment. Restricted by retrospective single-center design, inconsistent sampling timing, insufficient outcome events and lack of external validation, Netrin-1 is merely an investigational biomarker rather than a validated clinical prognostic assay.