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Ferroptosis contributes to hypoxic–ischemic brain injury in neonatal rats: Role of the SIRT1/Nrf2/GPx4 signaling pathway
AIMS: Hypoxic–ischemic brain injury (HIBI) often results in cognitive impairments. Herein, we investigated the roles of ferroptosis in HIBI and the underlying signaling pathways. METHODS: Ferrostatin‐1 (Fer‐1) or resveratrol (Res) treatments were administered intracerebroventricularly 30 min before...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627393/ https://www.ncbi.nlm.nih.gov/pubmed/36184790 http://dx.doi.org/10.1111/cns.13973 |
Sumario: | AIMS: Hypoxic–ischemic brain injury (HIBI) often results in cognitive impairments. Herein, we investigated the roles of ferroptosis in HIBI and the underlying signaling pathways. METHODS: Ferrostatin‐1 (Fer‐1) or resveratrol (Res) treatments were administered intracerebroventricularly 30 min before HIBI in 7‐day‐old rats. Glutathione peroxidase 4 (GPx4) expression, malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, and the expression of silent information regulator factor 2‐related enzyme 1 (SIRT1) and nuclear factor erythroid‐2‐related factor 2 (Nrf2) were measured after HIBI. Additionally, the weight ratio of left/right hemisphere, brain morphology, Nissl staining, and the Morris water maze test were conducted to estimate brain damage. RESULTS: At 24‐h post‐HIBI, GPx4 expression was decreased, and MDA concentration and iron content were increased in the hippocampus. HIBI led to mitochondrial atrophy, brain atrophy/damage, and resultant learning and memory impairments, which were alleviated by Fer‐1‐mediated inhibition of ferroptosis. Furthermore, Res‐mediated SIRT1 upregulation increased Nrf2 and GPx4 expression, thereby attenuating ferroptosis, reducing brain atrophy/damage, and improving learning and memory abilities. CONCLUSION: The results demonstrated that during HIBI, ferroptosis occurs via the SIRT1/Nrf2/GPx4 signaling pathway, suggesting it as a potential therapeutic target for inhibiting ferroptosis and ameliorating HIBI‐induced cognitive impairments. |
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