Targeting Ferroptosis Promotes Functional Recovery Through Mitigating White Matter Injury Following Acute Carbon Monoxide Poisoning

Abstract

Abstract Survivors suffering from acute carbon monoxide poisoning (ACMP) are apt to develop white matter injury (WMI). While, the mechanism that ACMP evokes WMI remains unclear. Given that ferroptosis plays an evident role in igniting oligodendrocyte damage to deteriorate WMI, exploring regimens to attenuate ferroptosis is a feasible approach to alleviate WMI post-ACMP. Here, the results indicated that ACMP induced WMI to evoke motor impairment resulting from the surplus iron and reactive oxygen species (ROS) accumulation after ACMP. And, the administration of ferrostatin-1 reduced iron and ROS deposition to repress ferroptosis, thereafter reducing WMI to promote motor recovery. Furthermore, the result demonstrated that the nuclear factor erythroid-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway was involved in attenuating ferroptosis resulting from the application of ferrostatin-1. The present study offers a rationale that targeting ferroptosis to alleviate WMI is a feasible therapeutic strategy for ACMP.