Aims
Hypoxic-ischemic brain injury (HIBI) often
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.
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.