Cerebrospinal Fluid MicroRNAs as Early Biomarker Candidates for Predicting Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) is frequently complicated by cerebral vasospasm, a major contributor to delayed cerebral ischemia and poor neurological outcomes. Early prediction remains challenging, and there is a critical need for reliable biomarkers. MicroRNAs (miRNAs) in cerebrospinal fluid (CSF) have emerged as promising indicators of acute neuropathological changes. This study aimed to evaluate CSF miRNA expression profiles in patients with aSAH to identify early predictors of vasospasm and improve clinical risk stratification. Methods: We conducted a prospective observational study involving 48 patients with aSAH (20 who developed vasospasm, 20 who did not) and eight healthy controls. A panel of 20 candidate miRNAs was analyzed in CSF samples collected on days 1 and 5 post-hemorrhage using quantitative real-time PCR. Expression differences between groups were assessed, and receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance. Results: Several miRNAs were differentially expressed in patients who developed vasospasm. On day 1, miR-221-3p and miR-183-5p were significantly upregulated (p = 0.014, p = 0.009), while miR-126, miR-29a, and miR-27b-3p were downregulated (p = 0.006, 0.021, 0.028) compared to controls. MiR-126 remained suppressed on day 5 (p = 0.002). These early changes showed high predictive accuracy (e.g., day-1 AUC for miR-221-3p ≈ 0.98, 95% CI 0.83–1.00). Compared to non-vasospasm patients, miR-221-3p was lower (0.12-fold), while miR-9-3p and miR-183-5p were higher (13.4-fold and 2.7-fold; all p < 0.01). MiR-24 and miR-21-5p correlated with more severe grades and poorer outcomes (p < 0.05). Conclusions: Specific CSF miRNAs—particularly miR-221-3p, miR-9-3p, and miR-183-5p—may serve as early biomarkers for vasospasm, warranting further validation in larger cohorts.