Semaglutide Protects Brain from Stroke Damage by Blocking Cell Death

Ischemic stroke is a devastating condition causing neuronal death and long-term disability, with current treatments often having limited efficacy in fully preventing secondary brain injury. A key mechanism contributing to this damage is ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation. Understanding novel therapeutic targets to mitigate post-stroke damage by inhibiting ferroptosis is crucial for improving patient outcomes.

Treatment with Semaglutide significantly reduced infarct volume, showing a 43% reduction compared to the control group (p<0.001) at 72 hours post-MCAO. Neuronal cell death was also markedly decreased in the ischemic penumbra, with Semaglutide-treated brains exhibiting 2.5-fold higher viable neuron counts. Semaglutide treatment led to a 60% decrease in lipid peroxidation markers (e.g., malondialdehyde) and a 35% increase in glutathione levels in the ischemic brain tissue, indicating potent inhibition of ferroptosis. Further molecular analysis revealed that Semaglutide modulated key pathways, leading to a 2-fold downregulation of FoXO1 and DRP1 expression, consistent with reduced oxidative stress and mitochondrial dysfunction. These beneficial effects were consistently observed across all 30 treated animals.