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Research Article: The predictive value of serum 25(OH)D, AQP4, and IL-4 levels for edema volume and clinical prognosis after traumatic brain injury

Date Published: 2026-04-21

Abstract:
This study aims to explore the associations between serum 25-hydroxyvitamin D (25(OH)D), aquaporin 4 (AQP4), and interleukin-4 (IL-4) levels with brain edema volume and outcomes in patients with traumatic brain injury (TBI). A cohort of 279 TBI patients, enrolled between January 2023 and December 2024, was analyzed. Serum levels of 25(OH)D, AQP4, and IL-4, as well as brain edema volume, were measured on days 1, 3, and 7 post-admission. Pearson correlation analysis was used to assess relationships between these serum markers and brain edema volume. Based on the 90-day follow-up outcome, patients were classified into a favorable outcome group ( n = 215) and a poor outcome group ( n = 64). Multivariate logistic regression was employed to identify factors influencing TBI outcomes. Serum 25(OH)D levels were highest on day 1 post-TBI, followed by day 3 and day 7 ( P < 0.05). In contrast, AQP4 and IL-4 levels, along with brain edema volume, were lowest on day 1 and increased significantly by days 3 and 7 ( P < 0.05). Serum 25(OH)D levels were inversely correlated with brain edema volume, while AQP4 and IL-4 levels exhibited a positive correlation ( P < 0.05). On days 1, 3, and 7, the favorable outcome group had higher serum 25(OH)D levels and lower AQP4 and IL-4 levels compared to the poor outcome group ( P < 0.05). Multivariate analysis revealed that serum 25(OH)D on day 1 and the Glasgow Coma Scale (GCS) score were associated with favorable outcomes, whereas IL-4 levels on day 1 independently predicted poor prognosis ( P < 0.05). ROC curve analysis demonstrated that all tested biomarkers had prognostic value, with serum 25(OH)D on day 1 showing the highest predictive accuracy. Serum levels of 25(OH)D, AQP4, and IL-4 are significantly associated with brain edema volume in TBI patients. Among these markers, serum 25(OH)D levels on the first day post-injury serve as the most reliable prognostic indicator of patient outcomes.

Introduction:
Traumatic brain injury (TBI) is a leading cause of death and disability globally, attracting significant attention due to its epidemiological characteristics and economic burden both worldwide and in China ( 1 ). According to the Global Burden of Disease study, 1,243,068 deaths from road traffic accidents were attributed to TBI in 2017. Despite improvements in mortality rates from road injuries, the incidence continues to rise, with notable geographical disparities ( 2 ). In China, TBI incidence and mortality…

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