TY - JOUR
T1 - Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage
AU - Wan, Jieru
AU - Ren, Honglei
AU - Wang, Jian
N1 - Funding Information:
Funding This research was supported by the National Institutes of Health (R56 NS096549, R01 NS102583 and R21 NS102899 to J. Wang), the American Heart Association (Grant-in-Aid, 17GRNT33660766 to J. W ang and 18POST33970007 to J. Wan), and a Stimulating and Advancing ACCM Research grant from the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University. Competing interests None declared. Patient consent for publication Not required. Provenance and peer review Not commissioned; externally peer reviewed. Data sharing statement No additional data are available.
Publisher Copyright:
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - Ferroptosis
KW - Intracerebral hemorrhage
KW - Iron toxicity
KW - Lipid peroxidation
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U2 - 10.1136/svn-2018-000205
DO - 10.1136/svn-2018-000205
M3 - Review article
C2 - 31338218
AN - SCOPUS:85060051541
SN - 2059-8688
VL - 4
SP - 93
EP - 95
JO - Stroke and Vascular Neurology
JF - Stroke and Vascular Neurology
IS - 2
ER -