ArticleMolecular neurobiology2025
Semaglutide Mitigates Ischemic Brain Injury by Inhibiting Ferroptosis via Modulation of FoXO1 and DRP1 Pathways.
Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- The Protective Mechanism of Continuous Theta Burst Stimulation in the Acute Phase of Stroke Through Modulation of the Calcineurin/AKT/FOXO1 Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- Semaglutide alleviates ovarian ferroptosis in polycystic ovary syndrome and is associated with reduced GPX4 promoter hypermethylation.Journal of molecular histology · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Multiple pathogenic processes contribute to cerebral ischemia-reperfusion injury (CIRI); however, their relative importance and sequence remain unclear, warranting further investigation. Although our previous studies showed that inhibiting ferroptosis mitigates brain damage after ischemic stroke, the crosstalk among intracellular pathways remains poorly understood. The protective effects of semaglutide, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in ischemic stroke have yet to be fully elucidated. In this study, bioinformatics analysis was conducted to predict the potential therapeutic mechanisms of semaglutide in CIRI, highlighting the involvement of the FoXO1-autophagy pathway and mitochondrial dynamics. A rat's middle cerebral artery occlusion/reperfusion (MCAO/R) model was established to validate these predictions. Histopathological examination demonstrated that semaglutide alleviated pathological damage and reduced neuronal apoptosis. Using Western blotting, RT-PCR, immunofluorescence, and ELISA, we assessed key markers-GLP-1R, FoXO1, Beclin1, DRP1, Mfn2, ATP, and ROS-in the ischemic penumbra. The results showed that semaglutide inhibited autophagy (Beclin1), suppressed mitochondrial fission (DRP1), promoted mitochondrial fusion (Mfn2), and improved mitochondrial function, as reflected by increased ATP production and reduced ROS levels. Furthermore, we investigated the involvement of FoXO1 and mitochondrial function in the regulation of ferroptosis. The findings suggest that semaglutide inhibits ferroptosis by activating GLP-1R, thereby modulating the intracellular FoXO1/GPX4 and DRP1/ACSL4 signaling pathways. In summary, semaglutide acts through GLP-1R to regulate FoXO1-mediated autophagy, mitochondrial dynamics, and ferroptosis, as well as to modulate DRP1-dependent mitochondrial fission and ferroptosis. Together, these mechanisms account for its protective effects against ischemic stroke.
Indexed as
Identifiers
40748430What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.