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.

miR-27a-3p protects against blood–brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11

“…However, the implications of miR-27a-3p down-regulation in the pathogenesis of post-ICH complications are unclear. Interestingly, a reduced level of miR-27a-3p was also observed in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage, and miR-27a-3p reduction was more prominent in those with vasospasm (15). These findings suggest a potential function of miR-27a-3p in the maintenance of cerebrovascular structure and function following hemorrhage.…”

Neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage

“…MicroRNAs are endogenous non-coding RNAs, approximately 18-25 nucleotides in length, which regulate transcriptional gene expression through binding the 3'-untranslated region of mRNAs and the non-translation region in the d-terminus (11). The majority of microRNA genes are located in the exonic, intronic and non-coding regions of the genome, and are transcribed into the microRNA primary transcript by RNA polymerase II, which results in the addition of a poly(A) tail (12).…”

Circulating MicroRNAs in Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage

“…Recently, studies of miRNAs in serum and cerebrospinal fluid identified biomarkers associated with occurrence of SAH, including miR‐92a, let‐7b, miR‐204‐5p, miR‐223‐3p, miR‐337‐5p, miR‐451a, miR‐489, miR‐508‐3p, miR‐514‐3p, miR‐516‐5p, miR‐548, miR‐599, miR‐937, miR‐1224‐3p and miR‐1301 . Our previous genomewide serum miRNA expression profiling also suggested that miR‐132‐3p and miR‐324‐3p could be potential biomarkers for SAH . Styllis and others investigated cerebrospinal fluid miRNAs in 10 SAH patients with and 10 without cerebral vasospasm and identified miR‐27a‐3p, miR‐516a‐5p, miR‐566, and miR‐1197 as potential biomarkers for cerebral vasospasm but not DCI .…”

“…Our previous genomewide serum miRNA expression profiling also suggested that miR‐132‐3p and miR‐324‐3p could be potential biomarkers for SAH . Styllis and others investigated cerebrospinal fluid miRNAs in 10 SAH patients with and 10 without cerebral vasospasm and identified miR‐27a‐3p, miR‐516a‐5p, miR‐566, and miR‐1197 as potential biomarkers for cerebral vasospasm but not DCI . The identification of miRNAs associated with DCI after SAH has been understudied, hindering understanding and development of therapeutic strategies for DCI after SAH.…”