Selenium Alleviates Cerebral Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Fusion and Ferroptosis.

Abstract

To clarify the potential role of selenium (Se) on cerebral ischemia/reperfusion (I/R) injury, we utilized mouse middle cerebral artery occlusion (MCAO) followed by reperfusion as an animal model and oxygen-glucose deprivation and reoxygenation (OGD/R) to treat N2a cells as a cell model, respectively. MCAO model was established in mice and then divided into different groups with or without Se treatment. TTC staining was used to observe whether the cerebral I/R modeling was successful, and the apoptosis level was determined by TUNEL staining. The expression of GPx-4 and p22phox was assessed by western blot. In vitro experiments, the OGD/R induced oxidative stress in N2a cells was assessed by levels of GSH/GSSG, malondialdehyde, superoxide dismutase and iron content, respectively. QRT-PCR was used to detect the mRNA levels of Cox-2, Fth1, Mfn1 and mtDNA in N2a cells. JC-1 staining and flow cytometry was performed to detect the mitochondrial membrane potential. Se treatment alleviated cerebral I/R injury and improved the survival rate of mice. Additionally, Se treatment apparently attenuated oxidative stress and inhibited iron accumulation in MCAO model mice and OGD/R model of N2a cells. In terms of its mechanism, Se could up-regulate Mfn1 expression to alleviate oxidative stress and ferroptosis by promoting mitochondrial fusion in vivo and vitro. These findings suggest that Se may have great potential in alleviating cerebral I/R injury.

• Authors: Yuanyuan Shi, Lijian Han, Xianxian Zhang, Lili Xie, Pinglei Pan, Fei Chen
• Journal: Neurochemical research (Neurochem Res) Vol. 47 Issue 10 Pg. 2992-3002 (Oct 2022) ISSN: 1573-6903 [Electronic] United States
• PMID: 35725978 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Iron
• Selenium

Topics

• Animals
• Apoptosis
• Brain Ischemia (metabolism)
• Disease Models, Animal
• Ferroptosis
• Infarction, Middle Cerebral Artery (drug therapy, metabolism)
• Iron
• Mice
• Mitochondrial Dynamics
• Oxidative Stress
• Reperfusion Injury (metabolism)
• Selenium (pharmacology, therapeutic use)