microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model

PLoS One. 2013 Jun 18;8(6):e66393. doi: 10.1371/journal.pone.0066393. Print 2013.

Abstract

To date, miRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models. Brain tissues were harvested at different reperfusion time points ranging from 0-168 hrs after middle cerebral artery occlusion using homologous emboli. MiRNA and mRNA expression profiles were investigated by microarray followed by multiple statistical analysis. Candidate transcripts were also validated by quantitative RT-PCR. Three specific groups of miRNAs were observed among a total of 346 differentially expressed miRNAs. miRNAs, miR-21, -142-3p, -142-5p, and -146a displayed significant upregulation during stroke recovery (48 hrs to 168 hrs) compared with those during acute phases (0 hrs to 24 hrs). On the other hand, an opposite trend was observed in the expression of miR-196a/b/c, -224 and -324-3p. Interestingly, miR-206, -290, -291a-5p and -30c-1*, positively correlated with the infarct sizes, with an initial increase up to 24hrs followed by a gradual decrease from 48 hrs to 168 hrs (R = 0.95). Taken together with the expression levels of corresponding mRNA targets, we have also found that Hedgehog, Notch, Wnt and TGF-β signaling pathways could play significant roles in stroke recovery and especially in neuronal repair.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal*
  • Disease Progression
  • Embolism / complications*
  • Male
  • Mice
  • MicroRNAs / physiology*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Stroke / etiology
  • Stroke / physiopathology*
  • Transcriptome

Substances

  • MicroRNAs

Grants and funding

This work was supported by research grants from National Medical Research Council, Singapore (NMRC-IRG/1279/2010: R-183-000-290-213) and National Research Foundation-Competitive Research Program on Stroke (NRF - CRP3 -2008-01: R-184-002-165-281), Singapore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.