414 Exploration and Validation of CSF miRNAs as Predictors of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Prospective Clinical Study

Abstract

INTRODUCTION: Approximately one-third of the patients who survive Aneurysmal Subrachnoid Hemorrhage (aSAH) have delayed cerebral ischemia (DCI) which contributes to poor clinical outcome. METHODS: A prospectively maintained clinical database was utilized under IRB approval for determination of clinical DCI and collection of biological samples. CSF samples were collected at 2-time points (<24 hours and 72 hours) post-aSAH from patients treated with external ventricular drainage. miRNAs were extracted from exosomes isolated from the CSF. In the first group of patients (exploratory phase), a CSF panel containing 84 miRNAs was analyzed using quantitative real-time PCR as an exploratory phase. Using the findings from the exploratory phase, we subsequently validated 26miRNAs in a second group of patients. RESULTS: We found three miRNAs i.e., miR-150-5p (p=0.02), miR-140-3p (p=0.03), and miR-26b-5p (p=0.01) were significantly upregulated in 72 vs 24 hours in patients that developed DCI. Moreover, we observed miR-451a (p=<0.0001) and miR-106a-5p (p=0.0001) were upregulated in No DCI at 72 hours. CONCLUSIONS: Our study identifies CSF exosomal miRNAs that could be crucial in progressing aSAH to DCI, and another set of miRNAs that possibly helps in aiding protection being entered into DCI. These miRNAs could be considered as potential biomarkers for DCI progression and prevention. Specifically miR-451a and miR-106a-5p may provide a protective role by reducing inflammation mediated by Matrix Metalloproteinases genes, thus crucial in the prevention of DCI. Further validation is important in additional patient cohorts.