Abstract

BackgroundThe methods currently available for diagnosis and prognosis of cerebral ischaemia still require further improvements. Micro-RNAs (small non-coding RNAs) have been recently reported as useful biomarkers in diseases such as cancer and diabetes. We therefore carried out microRNA (miRNA) profiling from peripheral blood to detect and identify characteristic patterns in ischaemic stroke.Methods/Principal FindingsThe ischaemic stroke patients aged between 18–49 years, characterized based on World Health Organization clinical criteria were further classified according to TOAST classification, a) Large-vessel atherosclerosis [n = 8] b) Small-vessel disease [n = 3] c) Cardioembolism [n = 5] d) Undetermined cause [n = 3]. The patients' functional status at the time of blood sampling (at the outpatient clinics) was evaluated with the modified Rankin Scale (mRS). Blood samples from normal (n = 5) individuals were used as controls. Total RNA extracted from whole blood was subjected to miroRNA profiling and real-time PCR analysis.miRNAs that are implicated in the endothelial/vascular function, erythropoiesis, angiogenesis and neural function showed differential expression profile as compared to the normal control. Interestingly, miRNAs that are involved in hypoxic conditions have also been found in our miRNA profiles.ConclusionWe demonstrate that the peripheral blood miRNAs and their profiles can be developed as biomarkers in diagnosis and prognosis of cerebral ischaemic stroke. The dysregulated miRNAs have been detectable even after several months from the onset of stroke in what is usually regarded as neurologically stable patients.

Highlights

  • MicroRNAs are tiny (,19–23 nt) non-coding RNA molecules that are currently being recognized as endogenous physiological regulators of gene expression

  • We demonstrate that the peripheral blood miRNAs and their profiles can be developed as biomarkers in diagnosis and prognosis of cerebral ischaemic stroke

  • The dysregulated miRNAs have been detectable even after several months from the onset of stroke in what is usually regarded as neurologically stable patients

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Summary

Introduction

MicroRNAs (miRNAs) are tiny (,19–23 nt) non-coding RNA molecules that are currently being recognized as endogenous physiological regulators of gene expression. These small RNAs are capable of controlling gene expression either by repression of translation/transcription (RNAi)[1] or by activation (RNAa) of transcription[2]. Using rodent models for ischemic stroke (MCAo), we have shown that miRNAs are temporally regulated during progression/reperfusion of cerebral ischemia and miRNAs in total blood could be used as diagnostic markers. In this study, using the blood samples obtained from young ischemic stroke patients (18 to 49 years) we have shown that besides the disease progression, the stroke subtype could be identified via the miRNA profiles. We carried out microRNA (miRNA) profiling from peripheral blood to detect and identify characteristic patterns in ischaemic stroke

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