Abstract DP287: Unbiased Screen of Circulating Cerebrospinal Fluid MicroRNA Identifies MiR-144-3p as a Predictor of SAH Long-term Outcome

Background: Cell-free circulating cerebrospinal fluid (CSF) miRNAs (miRs) function as posttranscriptional signals to remote organs and mediate diverse biological functions. In neurological diseases, the expression of CSF miRs may reflect distinct pathophysiological processes in the central nervous system (CNS) and predict SAH outcome. Here, we performed unbiased screening of cell-free CSF miR expression profiles in human SAH and identified potential miR biomarkers which predicts long term SAH outcome. Methods: In this prospective cohort study of 65 SAH patients and 15 controls, we stored serial CSF samples during acute phase SAH and assessed functional outcome, as measured by the modified Rankin Score (mRS) at 3 and 6 months post-SAH. Angiographic vasospasm was recorded if any cerebral vessel caliber decreased >50% on post-SAH day 7. Clinical and radiographic severity were evaluated by the Hunt and Hess (HH) and modified Fisher (miFisher) grades. Unbiased screen of 798 miRs was performed in cell-free CSF using Nanostring nCounter system with spike-in controls. Results: SAH cohort has a mean age of 55.8 years, 67.7% females, with 46.9% and 36.5% having unfavorable 3-month and 6-month outcome, respectively. 49.2% developed vasospasm. 66.2% had HH ≥3. We identified 795 miRs in both SAH subjects and controls. Compared with controls, CSF miR-144-3p is one of the most differentially expressed miRs with highest fold change in SAH CSF, and persistently increased in SAH compared to controls throughout post SAH days 1-5 (p values: 3.96e-25, 1.29e-21, 3.36e-24, respectively). Higher CSF miR-144-3p on post-SAH days 1, 3, and 5 is consistently associated with unfavorable outcomes at 3-month (p = 0.033, 0.046 and 0.009, respectively for days 1, 3 and 5) and at 6-month (p = 0.013, 0.020 and 0.053, respectively for days 1, 3 and 5). Conclusion: miR-144-3p is among the most abundantly expressed miR in the CSF of SAH patients. CSF miR-144-3p is significantly elevated in SAH compared to controls and might be associated with unfavorable long-term SAH outcome. It might be a candidate prognostic biomarker for SAH. Future studies are needed to understand potential mechanistic effects of miR-144-3p on SAH-associated brain injury.