AQP4 in cerebrospinal fluid correlates with severity and prognosis in moderate to severe traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite advances in acute care and neurological intensive care units, predicting long-term outcomes for patients with TBI remains challenging. Aquaporin-4 (AQP4) has emerged as a potential biomarker for assessing TBI severity and prognosis. Our goal is to evaluate AQP4 as a novel agent in the accurate diagnosis and prognosis of patients with TBI. This study included patients with TBI classified into mild (n = 80), moderate (n = 139), and severe (n = 96) groups based on Glasgow Coma Scale (GCS) scores. Cerebrospinal fluid (CSF) samples were collected at 1-, 7-, 14-, and 28-days postadmission, and AQP4 concentrations were measured using ELISA. The prognosis was evaluated using the Glasgow Outcome Scale (GOS) at 3 mo postinjury. The relationship between AQP4 levels and TBI severity, and their predictive value for patient outcomes, was analyzed. AQP4 levels in CSF peaked at 14 days postadmission and significantly decreased by 28 days in patients with both moderate and severe TBI. Higher AQP4 levels were consistently associated with worse prognosis at all measured time points. receiver operating characteristic (ROC) analysis revealed that AQP4 levels had predictive values at 1-, 7-, 14-, and 28-days postadmission, and the highest was shown at 14 days postadmission, with an area under the curve (AUC) of 0.79, sensitivity of 67.82%, and specificity of 83.78%. AQP4 in CSF is a promising biomarker for assessing TBI severity and predicting prognosis. Monitoring AQP4 levels could be an effective way to enhance prognostic accuracy, guide therapeutic interventions, and improve clinical decision-making in TBI management.NEW & NOTEWORTHY Our study is the first to comprehensively track dynamic changes in cerebrospinal fluid (CSF) aquaporin-4 (AQP4) levels in patients with moderate to severe traumatic brain injury. We show that AQP4 peaks at 14 days, correlates with injury severity, and consistently predicts 3-mo outcomes, with the strongest prognostic accuracy at day 14. These findings identify CSF AQP4 as a promising biomarker for assessing severity and prognosis, offering potential to improve early prediction and guide clinical decision-making in TBI management.