Ischemic stroke is a leading cause of death and long-term disability worldwide. It results from cerebral blood flow obstruction (ischemia) and, in some cases, the restoration of cerebral blood flow (reperfusion), triggering a cascade of pathophysiological events collectively known as the ischemic cascade and reperfusion injury, which leads to the activation of different regulated cell death types, and this review focuses on necroptosis and ferroptosis. Both pathways are closely linked to oxidative stress and contribute significantly to neuronal death and inflammation following ischemic stroke. Dysregulation of redox homeostasis, iron dyshomeostasis, glutathione depletion, and mitochondrial dysfunction are key events in neuronal damage. Understanding the interplay between oxidative stress and these pathways is crucial for developing effective neuroprotective therapies. This review highlights recent advances in understanding necroptosis and ferroptosis in ischemic stroke, proposing redox-targeted interventions as promising strategies to mitigate brain injury and improve outcomes in patients affected by this condition.
Monserrat et al. (Wed,) studied this question.