Piezo1 mechanosensitive ion channel in macrophages: a potential therapeutic target for intracerebral haemorrhage

Piezo1 is a mechanoreceptor cation channel that responds to various physical and environmental stimuli to facilitate an influx of cations, thereby converting physical or chemical triggers into electrochemical activity. Highly expressed on the surface of macrophages, Piezo1 can modulate macrophage polarisation and behaviour to ultimately regulate various inflammatory pathways. Given the role of pro-inflammatory signalling and the delayed recovery of patients with metabolic syndrome who develop intracerebral haemorrhage (ICH), Piezo1 could be a potential target for enhanced patient recovery and outcomes after ICH. Piezo1 ion channels are activated by increased environmental stiffness and chemical ligands, such as lipopolysaccharides. These channels initiate a signalling cascade and an increase in Ca 2+ influx in macrophages, which results in a variety of downstream effects, including cytoskeletal rearrangements for increased phagocytic activity and increased pro-inflammatory cytokine production. Piezo1 activation triggers the polarisation of macrophages into pro-inflammatory phenotypes while suppressing their conversion into inflammation-resolving phenotypes. In the context of ICH, both primary and pro-inflammatory secondary injury contribute to neurological damage. Suppressing Piezo1 attenuates brain oedema and neurological deficits after ICH, in part, by decreasing oligodendrocyte apoptosis and increasing cerebral blood flow. Given the unique characteristics of Piezo1 as a mechanosensitive ion channel, it shows promising potential as a target for ICH therapy. A timely conversion of pro-inflammatory macrophages into inflammation-resolving phenotypes via Piezo1 suppression may be the next step in improving post-ICH patient outcomes.