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Alterations in Apoptotic Pathways and Expression of Mir-134, Mir-181, and Mir-497 Induced by Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rat Model of Ischemic Brain Injury Publisher



Alizamir T1, 2 ; Jouzdani AF3, 4 ; Attari F5 ; Arab L6 ; Ashaari Z7 ; Komaki A8 ; Hassanzadeh G6, 9
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  2. 2. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
  3. 3. Neuroscience and Artificial Intelligence Research Group (NAIRG), Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  4. 4. USERN Office, Hamadan University of Medical Sciences, Hamadan, Iran
  5. 5. Institute for Cognitive Science Studies, Brain and Cognition Clinic, Tehran, Iran
  6. 6. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Physiology, School of Medicine, Mashhad University of Medicaid Sciences, Mashhad, Iran
  8. 8. Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  9. 9. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: IBRO Neuroscience Reports Published:2025


Abstract

Background: MicroRNAs (miRNAs) play crucial roles in regulating cell survival and signaling pathways. Mesenchymal stem cells (MSCs), particularly those derived from Wharton's Jelly (WJ-MSCs), have shown potential in promoting cell survival and reducing apoptosis. This study evaluates the effects of WJ-MSCs on miRNA expression and apoptosis markers in an ischemic brain injury model. Methods: Male Wistar rats (n = 30) were divided into control, sham, WJ-MSCs, Middle Cerebral Artery Occlusion (MCAO), and MCAO+WJ-MSCs groups. After 60 minutes of ischemia and 24 hours of reperfusion, WJ-MSCs were administered intracerebroventricularly. Post-surgical brain samples were analyzed using immunohistochemistry, TUNEL assay, and qRT-PCR to measure Bax/Bcl-2 ratios and miRNA (miR-497, miR-134, miR-181) expression in the cortex. Results: Immunohistochemistry revealed that the Bax/Bcl-2 ratio was significantly increased in the MCAO group, reflecting a pro-apoptotic state. In contrast, WJ-MSC treatment significantly reduced the Bax/Bcl-2 ratio in the ischemic cortex, suggesting a shift towards anti-apoptotic activity. Additionally, analysis of miRNA expression showed significantly elevated levels of miR-497, miR-134, and miR-181 in the brains of ischemic rats, which were associated with increased neuronal cell death. WJ-MSC treatment effectively modulated these miRNAs, resulting in a marked reduction in their expression. Furthermore, the TUNEL assay confirmed a substantial reduction in the number of apoptotic cells in the MCAO+WJ-MSCs group compared to the MCAO group. In the cortex, apoptotic cells were observed in WJ-MSC-treated rats, indicating enhanced neuronal survival. Conclusion: WJ-MSCs mitigate ischemic brain injury by modulating miRNA expression and apoptotic markers, promoting neuronal survival. These findings highlight their potential as a therapeutic strategy for ischemic brain injuries. © 2025
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