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

Abstract

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 h of intensive care unit admission associated with DCI using high-throughput proteomics. Methods: We conducted a prospective longitudinal study including 86 patients with aSAH, of whom 28 developed DCI. For this exploratory analysis, we matched eight patients who developed DCI with eight 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 false discovery rate correction. Results: We identified 15 significantly dysregulated proteins (P < 0.01) in patients with DCI. Key downregulated proteins included THSD1, CA3, and PROK1, which are associated with vascular integrity and endothelial function. Upregulated proteins included BGN, IFNG, and CSF2, which are related to innate immunity and neuroinflammation. Novel candidates, such as CLSTN3 and DOCK9, also showed altered expression. Protein-protein interaction and gene ontology enrichment analyses revealed involvement in inflammatory, immune, and metabolic pathways. Conclusions: Our findings suggest a distinct early molecular signature in patients with aSAH who develop DCI, characterized by proinflammatory and neurovascular dysfunction markers. These candidate biomarkers warrant further validation in larger cohorts and may provide preliminary insight into biological processes associated with DCI. Their potential clinical value will require confirmation in independent studies