Soluble Urokinase-Type Plasminogen Activator Receptor and Inflammatory Biomarker Response with Prognostic Significance after Acute Neuronal Injury – a Prospective Cohort Study

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) are severe conditions impacting individuals and society. Identifying reliable prognostic biomarkers for predicting survival or recovery remains a challenge. Soluble urokinase type plasminogen activator receptor (suPAR) has gained attention as a potential prognostic biomarker in acute sepsis. This study evaluates suPAR and related neuroinflammatory biomarkers in serum for brain injury prognosis. This prospective study included 31 aSAH, 30 IS, 13 TBI, and three healthy controls (n = 77). Serum samples were collected on average 5.9 days post-injury, analyzing suPAR, IL-1β, cyclophilin A, and TNFα levels using ELISA. Outcomes were assessed 90 days post-injury with the modified Rankin Scale (mRS), categorized as favorable (mRS 0-2) or unfavorable (mRS 3-6). Statistical analyses included 2-tailed t-tests, Pearson’s correlations, and machine learning linear discriminant analysis (LDA) for biomarker combinations. Elevated suPAR levels were found in brain injury patients compared to controls (p = 0.017). Increased suPAR correlated with unfavorable outcomes (p = 0.0018) and showed prognostic value (AUC = 0.66, p = 0.03). IL-1β levels were higher in the unfavorable group (p = 0.0015). LDA combinatory analysis resulted a fair prognostic accuracy with canonical equation = 0.775[suPAR] + 0.667[IL1-β] (AUC = 0.77, OR 0.296, sensitivity 93.1%, specificity 53.1%, p = 0.0007). No correlation was found between suPAR and CRP or infection status. Elevated suPAR levels in acute brain injury patients were associated with poorer outcomes, highlighting suPAR’s potential as a prognostic biomarker across different brain injury types. Combining IL-1β with suPAR improved prognostic accuracy, supporting a multimodal biomarker approach for predicting outcomes.