Iron Metabolism and Ferroptosis in Early Brain Injury after Subarachnoid Haemorrhage

Abstract

At present, it appears that the prognosis for subarachnoid haemorrhage (SAH), which has a high death and disability rate, cannot be greatly improved by medication or other treatment. Recent research suggests that different types of cell death are implicated in early brain injury (EBI) after SAH, and this has been recognised as a major factor impacting the prognosis of SAH. Ferroptosis, which is a recently identified imbalance of iron metabolism and programmed cell death triggered by phospholipid peroxidation, has been shown to be involved in EBI after SAH and is thought to have a significant impact on EBI. The decomposition of cleaved haemoglobin during SAH involves the release of enormous amounts of free iron, resulting in iron metabolism disorders. Potential therapeutic targets for the signalling pathways of iron metabolism disorders and ferroptosis after SAH are constantly being discovered. To serve as a guide for research into other possible therapeutic targets, this paper will briefly describe the mechanisms of dysregulated iron metabolism and ferroptosis in the pathogenesis of SAH and highlight how they are involved in the development and promotion of EBI in SAH.

Keywords: Apoptosis; Early brain injury; Ferroptosis; Iron metabolism; Neuroinflammation; Subarachnoid haemorrhage.

Fig. 1

Potential therapeutic targets for the signaling pathways of iron metabolism disorders and ferroptosis after SAH. (The abbreviations: TF: transferrin; TfR: transferrin receptor; FPN: Ferroportin; FSP-1: fibroblast specific protein-1; CoQ10R: coenzyme Q10 receptor; SLC7A11: Recombinant Solute Carrier Family 7, Member 11; Nrf2: Nuclear factor erythroid 2-related factor 2GSSG; GPX4: glutathione peroxidase 4; LIP: labile iron pool; PUFA: polyunsaturated fatty acids; ROS: reactive oxygen species; PL-OOH: phospholipid hydroperoxides; PE: phosphatidylethanolamine; ACSL4: Acyl-CoA synthetase long-chain family; LPCAT3: lyso-phosphatidylcholine acyltransferase-3; LOX: low-density lipoprotein receptor; NADP: nicotinamide adenine dinucleotide phosphate; NADPH: nicotinamide adenine dinucleotide phosphate; DMT1: divalent metal transporter 1;NCOA4: nuclear receptor coactivator-4;GSH: glutathione)