Piezo1 as a potential player in intracranial hemorrhage: from perspectives on biomechanics and hematoma metabolism.

Abstract

Intracranial hemorrhage (ICH) causes numerous neurological deficits and deaths worldwide each year, leaving a significant health burden on the public. The pathophysiology of ICH is complicated, and involves both primary and secondary injury. Hematoma, as the prime pathology of ICH, undergoes metabolism and triggers biochemical and biomechanical alterations in the brain, leading to secondary injury. Past endeavors mainly aimed at biochemical-initiated mechanisms for causing secondary injury have made limited progress in recent years, although ICH itself is also highly biomechanics-related. The discovery of the mechanical-activated cation channel Piezo1 provides a new avenue to further explore underlying mechanisms of secondary injury. The current article reviews the structure and gating mechanisms of Piezo1, its roles in the physiology/pathophysiology of neurons, astrocytes, microglia, and bone-marrow-derived macrophages, and especially its roles in erythrocytic turnover and iron metabolism, revealing a potential interplay between the biomechanics and biochemistry of hematoma in ICH. Collectively, these advances provide deeper insights into the secondary injury of ICH and lay the foundations for future research.