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Abstract Heme oxygenase 1 (HO-1) is a key enzyme involved in heme catabolism. Previous research showed that HO-1 tends to exacerbate neurological damage in the early stage of intracerebral hemorrhage (ICH). However, the specific mechanism remains unclear. Excessive iron accumulation, the primary product of HO-1 catabolism and heme metabolism, triggers neuronal ferroptosis, a key factor contributing to neurologic impairment following ICH. Our study aimed to examine the effects of HO-1 overexpression on neuronal ferroptosis in the early stages of ICH. Our findings demonstrated that HO-1 overexpression exacerbated the proinflammatory response of the microglia, which ultimately induced neuronal ferroptosis by promoting intracellular iron deposition. Furthermore, HO-1 overexpression disrupted the balance of iron metabolism in the microglia and promoted iron ion uptake in the neurons, leading to injury from lipid peroxidation and further contributing to neuronal ferroptosis. Ferrostatin-1 (Fer-1) treatment significantly mitigated the damage caused by HO-1 overexpression and improved neurologic function. Our study provides insights into the potential of targeting HO-1 to treat ICH by shedding light on the mechanisms underlying the aggravation of neuronal ferroptosis due to HO-1 overexpression in the early stages of ICH.
Liu et al. (Tue,) studied this question.