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A systematic review on the dual roles of microRNAs in ischemic stroke: mechanisms and effects

Nur Iffah Ishak1,2, Rosfaiizah Siran1,3, Wan Nor I'zzah Wan Mohamad Zain4

  • 1Multidisciplinary Initiative in Neuroscience Discovery and Science (MINDS), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia.

Peerj
|July 31, 2026
PubMed
Abstract

Insights

MicroRNAs (miRNAs) have dual roles in ischemic stroke, causing both damage and repair. Combination therapies show promise for stroke treatment, but clinical translation remains a challenge.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key regulators in ischemic stroke, exhibiting both protective and detrimental effects.
  • Understanding the dual roles of miRNAs is crucial for developing novel therapeutic strategies for cerebral ischemia.
  • This review examines miRNA expression, function, and dysregulation following ischemic stroke.

Purpose of the Study:

  • To systematically review preclinical studies on miRNA modulation in ischemic stroke.
  • To highlight key miRNAs, their dysregulated expression, and functional mechanisms post-stroke.
  • To assess the therapeutic potential of miRNA modulation for cerebral ischemia.

Main Methods:

  • Systematic review of 20 preclinical *in vivo* studies published within the last 5 years.
  • Studies were sourced from PubMed, Scopus, and Web of Science (WoS).
  • Inclusion criteria required miRNA expression levels, neurological function tests, and infarction volume data; descriptive synthesis was used due to study heterogeneity.

Main Results:

  • Ischemic stroke onset involves upregulation of detrimental miRNAs and downregulation of beneficial neuroprotective miRNAs.
  • Beneficial miRNAs promote angiogenesis, neurogenesis, and protect the blood-brain barrier, while detrimental miRNAs exacerbate injury.
  • Some miRNAs exhibit dual roles, influencing both apoptosis and neurogenesis.

Conclusions:

  • MiRNA modulation offers therapeutic potential, especially in combination therapies (e.g., dual miRNA or miRNA with other agents).
  • Despite promising preclinical data, significant translational barriers hinder the clinical application of miRNA-based stroke therapies.
  • MiRNAs' pleiotropic actions make them attractive multi-targeted candidates for stroke treatment, pending successful translation.
Keywords:
EffectIschemic strokeMechanismMicroRNANeuroprotection

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