Resveratrol pretreatment protects neurons from oxygen-glucose deprivation/reoxygenation and ischemic injury through inhibiting ferroptosis

Ferroptosis, a newly discovered iron-dependent cell death, is involved in brain ischemia-reperfusion injury. Iron scavengers or Ferroptosis inhibitors could reduce infarct volume and improve neurological function in mice. Resveratrol has neuroprotective and neurorestorative effects. However, it is unclear whether resveratrol can play a neuroprotective role via inhibiting Ferroptosis. Our study showed that resveratrol pretreatment had a similar effect with ferrostatin‑1, which inhibited neuronal ferroptosis-related changes, such as iron overload, damages of oxidation-reduction system, and destruction of mitochondrial structure, after oxygen-glucose deprivation/reoxygenation (OGD/R) and application of Ferroptosis inducers. In addition, middle cerebral artery occlusion/reperfusion (MCAO/R) injury in vivo also induced Ferroptosis, and resveratrol pretreatment could inhibit Ferroptosis and reduce degenerative neurons, cerebral ischemic damage and infarction volume. Our results are the first to indicate that resveratrol pretreatment might inhibit Ferroptosis induced by OGD/R and Ferroptosis inducers in neurons, and MCAO/R in rats.