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Therapeutic Potentials of MicroRNA-126 in Cerebral Ischemia

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Abstract

Stroke is a leading cause of death and disability worldwide. It is among the most common neurological disorders with an 8–10% lifetime risk. Ischemic stroke accounts for about 85% of all strokes and damages the brain tissue via various damaging mechanisms. Following cerebral ischemia, the disrupted blood–brain barrier (BBB) leads to cerebral edema formation caused by activation of oxidative stress, inflammation, and apoptosis, targeting primarily endothelial cells. Activation of the protective mechanisms might favor fewer damages to the neural tissue. MicroRNA (miR)-126 is an endothelial cell-specific miR involved in angiogenesis. MiR-126 orchestrates endothelial progenitor cell functions under hypoxic conditions and could inhibit ischemia-induced oxidative stress and inflammation. It alleviates the BBB disruption by preventing an augment in matrix metalloproteinase level and halting the decrease in the junctional proteins, including zonula occludens-1 (ZO-1), claudin-5, and occludin levels. Moreover, miR-126 enhances post-stroke angiogenesis and neurogenesis. This work provides a therapeutic perspective for miR-126 as a new approach to treating cerebral ischemia.

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Data Availability

All data are included in this published article.

Abbreviations

BBB:

Blood-brain barrier

BDNF:

Brain-derived neural factor

Ca+2 :

Calcium

COX-2:

Cyclooxygenase-2

FGF-2:

Fibroblast growth factor-2

HMGB1:

High mobility group box-1 protein

HO-1:

Hemoxygenase-1

ICAM1:

Intercellular adhesion molecule 1

IL:

Interleukin

MAPK:

Mitogen-activated protein kinase

MiR:

MicroRNA

MMP-9:

Matrix etalloproteinase-9

NF-κB:

Nuclear factor kappa B

NOS:

Nitric oxide synthesis

Nrf2:

Nuclear factor erythroid 2‑related factor 2

PIK3R2:

Phosphoinositide-3-kinase regulatory subunit 2

PTPN9:

Tyrosine-protein phosphatase non-receptor type 9

ROS:

Reactive oxygen species

SIRT1:

Sirtuin-1

SOD:

Superoxide dismutase

TLR4:

Toll-like receptor-4

TNF-α:

Tumor necrosis factor-alpha

VCAM1:

Vascular adhesion molecule 1

VEGF:

Vascular endothelial growth factor

ZO-1:

Zonula occludens-1

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Acknowledgements

We express our sincere gratitude for the Vice Chancellor’s support for Research, Mashhad University of Medical Sciences, Iran.

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Mashhad University of medical sciences.

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Authors and Affiliations

  1. Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Vahid Ebrahimi

  2. Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Hamidreza Rastegar-moghaddam & Abbas Mohammadipour

  3. Applied Biomedical Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Abbas Mohammadipour

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VE contributed to the drafting of the manuscript. AM and SHRM contributed to overall conceptual design, drafting and final edits and approval.

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Correspondence to Seyed Hamidreza Rastegar-moghaddam or Abbas Mohammadipour.

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Ebrahimi, V., Rastegar-moghaddam, S.H. & Mohammadipour, A. Therapeutic Potentials of MicroRNA-126 in Cerebral Ischemia. Mol Neurobiol 60, 2062–2069 (2023). https://doi.org/10.1007/s12035-022-03197-4

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  • DOI: https://doi.org/10.1007/s12035-022-03197-4

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