Abstract WP238: Novel Mirnas In Plasma And Cerebrospinal Fluid Of Intracerebral Hemorrhage

Abstract

Introduction: microRNAs (miRNAs) profiles in plasma and cerebrospinal fluid change in relation to cerebrovascular diseases and may serve as biomarkers or therapeutic targets of intracerebral hemorrhage (ICH). In this study, we examined the expression of novel and previously unreported miRNAs in ICH in plasma and cerebrospinal fluid (CSF) identified from miRNA sequencing. Methods: Patients with acute spontaneous ICH (n=8) were consented and peripheral whole blood were collected within 48 hours of ICH onset and processed for plasma and peripheral blood mononuclear cells (PBMC). CSF was obtained from an external ventricular drain (EVD). Six novel miRNAs were selected from miR-Seq analysis and further validated for their expression in ICH plasma/CSF, PBMC RNA and normal control plasma/CSF. Total RNA was used for real-time PCR validation of novel miRNAs using custom locked-nucleic acid (LNA) assay. Demographic and clinical data were collected. Results: miRNA-seq comparison between ICH plasma and CSF identified 19 and 30 differentially expressed miRNA (p<0.05), of which 9 and 7 novel miRNAs were identified in plasma and CSF, respectively. PC-5p-218_26568 was identified in ICH CSF, ICH PBMC and weakly in ICH plasma and normal plasma, but not in normal CSF. PC-5p-585_8337 was identified in ICH CSF and plasma, but not in normal CSF, plasma or ICH PBMC. PC-3p-4244_570 was found in CSF and plasma ICH patients and normal controls, exhibiting a 4-fold and 11-fold higher in ICH CSF and plasma than normal controls. It was also identified in ICH PBMC. PC-5p-1115_3460 was detected in normal plasma but not in ICH plasma, whereas PC-5p-6497_338 was found in ICH plasma but not in normal plasma and CSF. Lastly, PC-3p-3144_857 was found in ICH plasma and ICH PBMC and not in CSF. Conclusion: We identified distinct differences in miRNAs expression in healthy and ICH plasma and CSF. Further studies are underway on the gene targets and utility of these miRNAs as therapeutic targets or biomarkers of ICH.