Abstract W MP29: CSF MicroRNA-181b is Associated With Poor 6-Month Outcome Following Subarachnoid Hemorrhage

Abstract

Background: Early brain injury and vasospasm (VSP) in subarachnoid hemorrhage (SAH) are associated with inflammation and release of TNFα, which correlates with poor SAH clinical outcome. TNFα regulates the expression of microRNA (miR) 181b, which mediates NF-κB signaling and is known to exacerbate ischemic stroke in animal models. MiRs have higher stability in biological fluids than peptides and may be candidate clinical biomarkers. We hypothesize that miR-181b is present in SAH CSF and may be associated with SAH outcome. Methods: We prospectively enrolled consecutive SAH subjects, banked serial CSF samples, and evaluated their modified Rankin scores (mRS) via telephone follow-up every 3 months. Poor functional outcome was defined as mRS>2. Angiographic VSP was defined as >50% reduction in caliber of any vessel on post-SAH day 7 cerebral angiogram. In 54 SAH subjects, we compared CSF miR-181b and 26a (as control) by quantitative PCR on post-SAH day 3 with respect to VSP and outcome using Student’s t-test after log-transformation of data with non-normal distribution. Associations were measured using Pearson’s or Spearman’s correlation depending on data distribution. Results: Twenty-seven subjects (50%) developed VSP and 21 (39%) had poor 6-month outcome. MiRs-181b and 26a were consistently measurable in SAH CSF, and miR levels were not associated with Hunt and Hess or Fisher grades. Elevation of CSF miR-181b was associated with poor 6-month outcome in SAH (p=0.04). CSF miR-181b inversely correlated with blood TNFα (r=0.74, p=0.0001). CSF miR-181b was not associated with VSP. CSF miR-26a was not associated with VSP or with clinical outcome in SAH. Conclusion: MiR-181b is present in human CSF after SAH and early elevation of CSF miR-181b is associated with poor 6-month outcome but not with VSP after SAH. Lack of association between control miR-26a and outcome suggests that association between miR-181b and SAH outcome is not due to a non-specific miR surge in more severe cases. Inverse correlation between blood TNFα and CSF miR-181b suggests TNFα may mediate miR-181b release into CSF. Future mechanistic studies on the role of miR-181b in SAH-related brain injury and validation studies in larger cohorts are necessary to understand the role of miR-181b as a SAH biomarker.