Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage

Jieru Wan, Honglei Ren, Jian Wang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalStroke and Vascular Neurology
DOIs
StateAccepted/In press - Jan 1 2019

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Cerebral Hemorrhage
Lipid Peroxidation
Iron
Reactive Oxygen Species
Cell Death
Stroke
Chelation Therapy
Iron Overload
Membrane Lipids
Brain Injuries
Nucleic Acids
Membrane Proteins
Oxidative Stress
Therapeutics
Morbidity
Lipids
Mortality

Keywords

  • ferroptosis
  • intracerebral hemorrhage
  • iron toxicity
  • lipid peroxidation

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage. / Wan, Jieru; Ren, Honglei; Wang, Jian.

In: Stroke and Vascular Neurology, 01.01.2019.

Research output: Contribution to journalArticle

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