title: miRNA expression profiling of cerebrospinal fluid in patients with aneurysmal subarachnoid hemorrhage.
abstract: OBJECTIVE MicroRNAs (miRNAs) regulate gene expression and therefore play important roles in many physiological and pathological processes. The aim of this pilot study was to determine the feasibility of extraction and subsequent profiling of miRNA from CSF samples in a pilot population of aneurysmal subarachnoid hemorrhage patients and establish if there is a distinct CSF miRNA signature between patients who develop cerebral vasospasm and those who do not. METHODS CSF samples were taken at various time points during the clinical management of a subset of SAH patients (SAH patient samples without vasospasm, n = 10; SAH patient samples with vasospasm, n = 10). CSF obtained from 4 patients without SAH was also included in the analysis. The miRNA was subsequently isolated and purified and then analyzed on an nCounter instrument using the Human V2 and V3 miRNA assay kits. The data were imported into the nSolver software package for differential miRNA expression analysis. RESULTS From a total of 800 miRNAs that could be detected with each version of the miRNA assay kit, a total of 691 miRNAs were communal to both kits. There were 36 individual miRNAs that were differentially expressed (p < 0.01) based on group analyses, with a number of miRNAs showing significant changes in more than one group analysis. The changes largely reflected differences between non-SAH and SAH groups. These included miR-204-5p, miR-223-3p, miR-337-5p, miR-451a, miR-489, miR-508-3p, miR-514-3p, miR-516-5p, miR-548 m, miR-599, miR-937, miR-1224-3p, and miR-1301. However, a number of miRNAs did exclusively differ between the vasospasm and nonvasospasm SAH groups including miR-27a-3p, miR-516a-5p, miR-566, and miR-1197. CONCLUSIONS The findings indicate that temporal miRNA profiling can detect differences between CSF from aneurysmal SAH and non-SAH patients. Moreover, the miRNA profile of CSF samples from patients who develop cerebral vasopasm may be distinguishable from those who do not. These results provide a foundation for future research at identifying novel CSF biomarkers that might predispose to the development of cerebral vasospasm after SAH and therefore influence subsequent clinical management.
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital.|Department of Neurosurgery, The Royal Melbourne Hospital.
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Stylli
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital.|Department of Neurosurgery, The Royal Melbourne Hospital.
authors.forename: Alexios A
authors.initials: AA
authors.lastname: Adamides
authors.affiliation: ACRF Translational Research Laboratory, The Department of Research, The Royal Melbourne Hospital; and.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Koldej
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital.
authors.forename: Rodney B
authors.initials: RB
authors.lastname: Luwor
authors.affiliation: ACRF Translational Research Laboratory, The Department of Research, The Royal Melbourne Hospital; and.
authors.forename: David S
authors.initials: DS
authors.lastname: Ritchie
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Ziogas
authors.affiliation: Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital.|Department of Neurosurgery, The Royal Melbourne Hospital.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000628:therapy; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: CVP = central venous pressure; CVS = cerebral vasospasm; MTI = miRNA-target interaction; SAH = subarachnoid hemorrhage; aSAH = aneurysmal SAH; cerebrospinal fluid; miRNA; miRNA = microRNA; miRTarBase = microRNA-target interactions database; subarachnoid hemorrhage; vascular disorders; vasospasm