The mechanism of ferroptosis in early brain injury after subarachnoid hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) is a cerebrovascular accident with an acute onset, severe disease characteristics, and poor prognosis. Within 72 hours after the occurrence of SAH, a sequence of pathological changes occur in the body including blood-brain barrier breakdown, cerebral edema, and reduced cerebrovascular flow that are defined as early brain injury (EBI), and it has been demonstrated that EBI exhibits an obvious correlation with poor prognosis. Ferroptosis is a novel programmed cell death mode. Ferroptosis is induced by the iron-dependent accumulation of lipid peroxides and reactive oxygen species (ROS). Ferroptosis involves abnormal iron metabolism, glutathione depletion, and lipid peroxidation. Recent study revealed that ferroptosis is involved in EBI and is significantly correlated with poor prognosis. With the gradual realization of the importance of ferroptosis, an increasing number of studies have been conducted to examine this process. This review summarizes the latest work in this field and tracks current research progress. We focused on iron metabolism, lipid metabolism, reduction systems centered on the GSH/GPX4 system, other newly discovered GSH/GPX4-independent antioxidant systems, and their related targets in the context of early brain injury. Additionally, we examined certain ferroptosis regulatory mechanisms that have been studied in other fields but not in SAH. A link between death and oxidative stress has been described. Additionally, we highlight the future research direction of ferroptosis in EBI of SAH, and this provides new ideas for follow-up research.

Relationship between baseline bicarbonate and 30-day mortality in patients with non-traumatic subarachnoid hemorrhage

“…SAH is a common type of stroke in the ICU and has a high mortality rate. Recent research has revealed a strong correlation between EBI and a bad prognosis in SAH patients ( 4 ). After SAH, there will be several alterations in cerebral perfusion.…”

“…Earlier research believed that post-SAH cerebral vasospasm was thought to be a major factor in the prognosis of the disease, but the clinical treatment of cerebral vasospasm did not significantly improve the neurological outcome of patients ( 3 ). In recent years, most experimental and clinical studies have focused on the pathophysiological mechanism of early brain injury (EBI), and it is believed that this stage may be closely related to poor outcomes of patients ( 4 ). EBI is defined as the pathological events in the first 72 h after SAH, which has become a research hotspot in the field of neurology ( 5 ).…”

Lower Serum Iron Level Predicts Postoperative Global Cerebral Edema Following Aneurysmal Subarachnoid Hemorrhage

“…However, obtaining intracerebral iron accumulation through more invasive and risky procedures potentially restricts its widespread popularity. Moreover, other relevant indicators of iron metabolism were not included in the analysis (relevant data were not collected in this study) [ 41 ], which might also affect the accuracy of the findings. The results should be interpreted cautiously and extended to other populations due to differences in metabolic levels, such as iron metabolism between races.…”

Environmentally relevant levels of Cd and Mo coexposure induces ferroptosis and excess ferritinophagy through AMPK/mTOR axis in duck myocardium

“…Ferroptosis is induced through disequilibrium between antioxidation and oxidation. Additionally, previous document has proved that ferroptosis can contribute to occurrence and development of multiple diseases, including strokes, liver insufficiency, renal insufficiency, tumors, and cardiomyopathy 18 …”