Ferroptosis in Central Nervous System Hypoxia-Ischemia

Millions of people suffer from acute hypoxic-ischemic brain injuries (HIBIs) such as stroke and neonatal HIBI worldwide each year, resulting in significant mortality and lifelong morbidity. Therapeutic options for HIBI remain limited, but many investigators are actively seeking out novel therapies based on our evolving understanding of the pathophysiology. Ferroptotic cell death has recently been demonstrated to play a significant part in the complex cellular injury resulting after HIBI. This chapter will discuss the current literature evaluating the role of ferroptosis-related reactive oxygen species release and lipid peroxidation in the pathophysiology of HIBI. Based on the current mechanistic understanding, several investigators have begun to develop interventions for HIBI that target the ferroptosis pathways. As such, this chapter will also discuss many of the ferroptosis inhibitors that have shown neuroprotective effects in cell culture and animal models of HIBI.