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MicroRNA miR-21 Decreases Post-stroke Brain Damage in Rodents

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Abstract

Due to their role in controlling translation, microRNAs emerged as novel therapeutic targets to modulate post-stroke outcomes. We previously reported that miR-21 is the most abundantly induced microRNA in the brain of rodents subjected to preconditioning-induced cerebral ischemic tolerance. We currently show that intracerebral administration of miR-21 mimic decreased the infarct volume and promoted better motor function recovery in adult male and female C57BL/6 mice subjected to transient middle cerebral artery occlusion. The miR-21 mimic treatment is also efficacious in aged mice of both sexes subjected to focal ischemia. Mechanistically, miR-21 mimic treatment decreased the post-ischemic levels of several pro-apoptotic and pro-inflammatory RNAs, which might be responsible for the observed neuroprotection. We further observed post-ischemic neuroprotection in adult mice administered with miR-21 mimic intravenously. Overall, the results of this study implicate miR-21 as a promising candidate for therapeutic translation after stroke.

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Data Availability

Authors will provide all data when requested following the procedures and rules governed by the University of Wisconsin and William S. Middleton VA Hospital Research Center of Madison, WI.

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Acknowledgements

This work was supported by Award 1I01-BX005127-01 from the U.S. Department of Veterans Affairs Biomedical Research Laboratory Research and Development Service of the VA Office of Research Development and the Dept. of Neurological Surgery, UW-Madison. MSL received a SciMedGRS/Centennial Graduate Student Scholarship.

Funding

This work was partially supported by Award 1I01-BX005127-01 from the U.S. Department of Veterans Affairs Biomedical Research Laboratory Research and Development Service of the VA Office of Research Development and the Dept. of Neurological Surgery, UW-Madison. Dr. Vemuganti is the recipient of a Research Career Scientist award (# IK6BX005690) from the US Department of Veterans Affairs. Mary Lopez received a SciMedGRS/Centennial Graduate Student Scholarship.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of Wisconsin, Madison, WI, 53792, USA

    Mary S. Lopez, Kahlilia C. Morris-Blanco, Nancy Ly, Carly Maves, Robert J. Dempsey & Raghu Vemuganti

  2. Cell & Molecular Pathology Training Program, University of Wisconsin, Madison, WI, 53792, USA

    Mary S. Lopez & Raghu Vemuganti

  3. William S. Middleton Memorial Veterans Hospital, Madison, WI, USA

    Raghu Vemuganti

Authors
  1. Mary S. Lopez
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  2. Kahlilia C. Morris-Blanco
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  3. Nancy Ly
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  4. Carly Maves
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  5. Robert J. Dempsey
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  6. Raghu Vemuganti
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Contributions

MSL and KCM-B, NL, and CM conducted the experiments and analyzed the data. RV and RJD conceptualized the project. MSL and RV drafted the paper.

Corresponding author

Correspondence to Raghu Vemuganti.

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All animal protocols were approved by the Research Animal Resources and Care Committee of the University of Wisconsin-Madison, and animals were cared for in accordance with the Guide for the Care and Use of Laboratory Animals (U.S. Department of Health and Human Services Publication 86–23, revised). Studies were conducted and reported in accordance to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines.

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Lopez, M.S., Morris-Blanco, K.C., Ly, N. et al. MicroRNA miR-21 Decreases Post-stroke Brain Damage in Rodents. Transl. Stroke Res. 13, 483–493 (2022). https://doi.org/10.1007/s12975-021-00952-y

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  • DOI: https://doi.org/10.1007/s12975-021-00952-y

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