Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage.

Abstract

Intracerebral haemorrhage (ICH) is a devastating type of stroke with high mortality and morbidity. However, we have few options for ICH therapy and limited knowledge about post-ICH neuronal death and related mechanisms. In the aftermath of ICH, iron overload within the perihaematomal region can induce lethal reactive oxygen species (ROS) production and lipid peroxidation, which contribute to secondary brain injury. Indeed, iron chelation therapy has shown efficacy in preclinical ICH studies. Recently, an iron-dependent form of non-apoptotic cell death known as ferroptosis was identified. It is characterised by an accumulation of iron-induced lipid ROS, which leads to intracellular oxidative stress. The ROS cause damage to nucleic acids, proteins and lipid membranes, and eventually cell death. Recently, we and others discovered that ferroptosis does occur after haemorrhagic stroke in vitro and in vivo and contributes to neuronal death. Inhibition of ferroptosis is beneficial in several in vivo and in vitro ICH conditions. This minireview summarises current research on iron toxicity, lipid peroxidation and ferroptosis in the pathomechanisms of ICH, the underlying molecular mechanisms of ferroptosis and the potential for combined therapeutic strategies. Understanding the role of ferroptosis after ICH will provide a vital foundation for cell death-based ICH treatment and prevention.

• Authors: Jieru Wan, Honglei Ren, Jian Wang
• Journal: Stroke and vascular neurology (Stroke Vasc Neurol) Vol. 4 Issue 2 Pg. 93-95 (Jul 2019) ISSN: 2059-8696 [Electronic] England
• PMID: 31338218 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Iron Chelating Agents
• Iron

Topics

• Animals
• Brain (drug effects, metabolism, pathology)
• Cerebral Hemorrhage (drug therapy, metabolism, pathology)
• Ferroptosis (drug effects)
• Humans
• Iron (blood, metabolism)
• Iron Chelating Agents (therapeutic use)
• Lipid Peroxidation (drug effects)
• Oxidative Stress (drug effects)