Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

MiR-124 alleviates cerebral ischemia-reperfusion injury by targeting SLC1A5 to inhibit neuronal ferroptosis

Articles in Press

Document Type : Original Article

Authors
Zhu Yizhen 1
Jiang Qian 2
Long Tingting 2
Huang Tao 2
Zhu Junde 2
1 Class 5, Grade 2023, Clinical Medicine, Guizhou Medical University, Gui’an New District, Guizhou 561113, People’s Republic of China
2 Department of Anatomy and Neurobiology, Guizhou Medical University School of Basic Medicine, Gui’an New District, Guizhou 561113, People’s Republic of China
10.22038/ijbms.2026.93806.20223
Abstract
Objective(s): This study aimed to investigate whether miR-124 alleviates neurological injury in cerebral ischemia-reperfusion injury (CIRI) mice by targeting Solute Carrier Family 1 Member 5 (SLC1A5) to regulate ferroptosis.
Materials and Methods: One hundred twenty male C57BL/6 mice were randomly assigned to Sham, CIRI model, miR-124 mimic, miR-124 inhibitor, miR-124 vector, and Ferrostatin-1 (Fer-1) groups. One week before modeling, the viral groups received 2.0 μl of the corresponding viral vector via right lateral ventricle injection. Additionally, the Fer-1 group received intraperitoneal injections of ferrostatin-1 (5.0 mg/kg). Following the establishment of the MCAO model by the wire occlusion method. At different time points, the Longa method was employed to assess the degree of neurological deficit. TTC staining was used to detect cerebral infarction volume. ELISA was applied to measure changes in SOD, MDA, GSH, and Fe²⁺. qRT-PCR was utilized to detect the expression levels of miR-124, SLC1A5, and GPX4, and Immunohistochemistry was detected SLC1A5-positive cells. Finally, the miR-124/SLC1A5 interaction was predicted by bioinformatics and validated by a dual-luciferase assay and western blot.
Results: Compared with the sham group, the CIRI group showed reduced neurological scores, elevated MDA/Fe²⁺, and decreased SOD/GSH/GPX4. miR-124 mimic treatment significantly improved these parameters, similar to Fer-1, whereas miR-124 inhibition exacerbated injury and increased SLC1A5 expression. Dual-luciferase assay confirmed SLC1A5 as a direct target of miR-124.
Conclusion: Collectively, these data indicate that MiR-124 attenuates CIRI-induced neurological damage, potentially by targeting SLC1A5 to inhibit ferroptosis, as evidenced by up-regulation of GPX4 and GSH.
Keywords
Cerebral Ischemia
Ferroptosis
MiR-124
Neuroprotection
Reperfusion Injury
Solute carrier family 1 member 5
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 27 July 2026