Neuroinflammatory diseases triggered by cerebral hemorrhage: microglial iron accumulation and ferroptosis

After a cerebral hemorrhage (CH), heme oxygenase-1 (HO-1) catalyzes the conversion of heme to release Fe²⁺. Microglia are the primary cells responsible for immune function in the brain. Upon the uptake of heme and iron ions, microglia are activated, leading to the subsequent release of inflammatory mediators and reactive oxygen species. Neuroinflammation and oxidative stress are common features of various brain diseases. Cerebral hemorrhage can trigger microglial iron accumulation and ferroptosis, which in turn leads to neuroinflammation and oxidative stress imbalance in the brain. Therefore, inhibiting microglial iron accumulation and ferroptosis alleviates cerebral hemorrhage-mediated neural damage and counteracts various brain diseases induced by it. We propose that the occurrence of many brain diseases is influenced by the location of cerebral microbleeds, suggesting that cerebral microbleeds may be a high-risk factor for inducing these diseases.