Biomarker Differences in Aneurysmal Subarachnoid Hemorrhage: A Comparative Study of Patients With and Without Delayed Cerebral Ischemia

Background: Delayed cerebral ischemia (DCI) is a major cause of morbidity following aneurysmal subarachnoid hemorrhage (aSAH), yet early prediction remains challenging. This study aimed to identify blood-based protein biomarkers within 24 hours of ICU admission associated with DCI using high-throughput proteomics. Methods: We conducted a prospective longitudinal study including 86 aSAH patients, of whom 28 developed DCI. For this exploratory analysis, we matched 8 patients who developed DCI with 8 controls without DCI based on age, sex, and severity scores. Plasma samples were analyzed using the Olink® Explore 3072 platform targeting 2,943 proteins. Differential expression analysis was performed using linear Bayesian models with FDR correction. Results: We identified 15 significantly dysregulated proteins (p < 0.01) in DCI patients. Key downregulated proteins included THSD1, CA3, and PROK1—associated with vascular integrity and endothelial function. Upregulated proteins included BGN, IFNG, and CSF2—related to innate immunity and neuroinflammation. Novel candidates such as CLSTN3 and DOCK9 also showed altered expression. Protein-protein interaction and GO enrichment analyses revealed involvement in inflammatory, immune, and metabolic pathways. Conclusions: Our findings suggest a distinct early molecular signature in aSAH patients who develop DCI, characterized by pro-inflammatory and neurovascular dysfunction markers. These candidate biomarkers warrant further validation in larger cohorts and may guide early risk stratification and therapeutic interventions.