Abstract

MicroRNAs have been identified as key regulators of gene expression and thus their potential in disease diagnostics, prognosis and therapy is being actively pursued. Deregulation of microRNAs in cerebral pathogenesis has been reported to a limited extent in both animal models and human. Due to the complexity of the pathology, identifying stroke specific microRNAs has been a challenge. This study shows that microRNA profiles reflect not only the temporal progression of stroke but also the specific etiologies. A panel of 32 microRNAs, which could differentiate stroke etiologies during acute phase was identified and verified using a customized TaqMan Low Density Array (TLDA). Furthermore we also found 5 microRNAs, miR-125b-2*, -27a*, -422a, -488 and -627 to be consistently altered in acute stroke irrespective of age or severity or confounding metabolic complications. Differential expression of these 5 microRNAs was also observed in rat stroke models. Hence, their specificity to the stroke pathology emphasizes the possibility of developing these microRNAs into accurate and useful tools for diagnosis of stroke.

Highlights

  • Cerebral ischemia or stroke represents one of the leading causes of mortality and serious long-term disability worldwide with a projected increase of 24.9% by 2030 [1]

  • Blood based miRNAs could provide an additional tool for an accurate analysis to assess diagnosis of stroke patients

  • Based on patient blood miRNA profiles, our study identified a panel of 32 miRNAs that could accurately distinguish stroke subtypes

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Summary

Introduction

Cerebral ischemia or stroke represents one of the leading causes of mortality and serious long-term disability worldwide with a projected increase of 24.9% (from 2010) by 2030 [1]. The diagnostic and prognostic powers are very often limited in stroke management, in comparison to cardiovascular ischemia [2,3] Protein biomarkers such as C-reactive protein, interleukin-6, matrix metallopeptidase 9, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 have been suggested as additional diagnostic tools. Their specificity and ability to distinguish between acute stroke and its associated risk factors or even stroke mimics is uncertain [4]. Though several groups have reported on altered expression of miRNAs. during ischemic stroke [14,15], the specificity to acute stroke pathology or exclusion of confounding risk factors have not been established. The miRNAs identified in this study hold the diagnostic potential for stroke as well as etiology differentiation

MicroRNAs as Biomarkers of Acute Stroke
Experimental Section
Total RNA Isolation
Quantitative PCR
Conclusions

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