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Neuroprotective Therapeutic Potential of microRNA-149-5p against Murine Ischemic Stroke

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Abstract

Ischemic stroke resulting from blockade of brain vessels lacks effective treatments, prompting exploration for potential therapies. Among promising candidates, microRNA-149 (miR-149) has been investigated for its role in alleviating oxidative stress, inflammation, and neurodegeneration associated with ischemic conditions. To evaluate its therapeutic effect, male Wistar rats were categorized into five groups, each consisting of 27 rats: sham, MCAO, lentiviral control, lentiviral miR-149, and miR149-5p mimic. Treatments were microinjected intracerebroventricularly (ICV) (right side), and ischemia was induced using middle cerebral artery occlusion (MCAO) procedure. Post-MCAO, neurological function, histopathological changes, blood-brain barrier (BBB) permeability, cerebral edema, and mRNA levels of Fas ligand (Faslg) and glutamate ionotropic NMDA receptor 1 (GRIN1) were assessed, alongside biochemical assays. MiR-149 administration improved neurological function, reduced brain damage, preserved BBB integrity, and attenuated cerebral edema. Upregulation of miR149-5p decreased Faslg and GRIN1 expression in ischemic brain regions. MiR-149 also reduced oxidative stress, enhanced antioxidant activity, decreased caspase-1 and − 3 activity, and modulated inflammatory factors in ischemic brain regions. Moreover, DNA fragmentation as an index of cell death decreased following miR-149 treatment. In conclusion, the study underscores miR-149 potential as a neuroprotective agent against ischemic stroke, showcasing its efficacy in modulating various mechanisms and supporting its candidacy as a promising therapeutic target for innovative strategies in stroke treatment.

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Acknowledgements

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Funding

This study received support from a grant (No. 99025398) provided by the Iran National Science Foundation (INSF).

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Authors and Affiliations

  1. Department of Animal Science and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

    Samira Vahidi, Mohammad-Reza Bigdeli & Salma Ahmadloo

  2. Institute for Cognitive and Brain Science, Shahid Beheshti University, Tehran, Iran

    Mohammad-Reza Bigdeli

  3. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

    Hosein Shahsavarani

  4. Neurophysiology Research Center, Shahed University, Tehran, Iran

    Mehrdad Roghani

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  1. Samira Vahidi
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  2. Mohammad-Reza Bigdeli
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Contributions

The study’s conception and design were developed by M.R.B. and M.R., with H.S. and S.A. providing support in procuring necessary equipment. S.V. carried out the experiments, analyzed the data, and drafted the initial manuscript. The culmination of the manuscript was a collaborative effort, with all authors contributing equally to its refinement.

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Correspondence to Mohammad-Reza Bigdeli or Mehrdad Roghani.

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The animal experiments adhered to the National Institute of Health Guide for the Care and Use of Laboratory Animals. The study protocol received approval from the Research Ethics Committees of Shahid Beheshti University (IR.SBU.REC.1400.100), ensuring compliance with ethical standards in research involving laboratory animals.

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Vahidi, S., Bigdeli, MR., Shahsavarani, H. et al. Neuroprotective Therapeutic Potential of microRNA-149-5p against Murine Ischemic Stroke. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04159-8

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