Ferrostatin-1 Alleviates White Matter Injury Via Decreasing Ferroptosis Following Spinal Cord Injury

Abstract Spinal cord injury (SCI), a devastating neurological impairment, ubiquitously imposes a long-term psychological stress and high socioeconomic burden for the suffers and their family. To date, recent researchers have paid arousing attention to white matter injury and uncovering the underlying mechanism post-SCI. Ferroptosis, to our knowledge, has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. However, its role in white matter damage after SCI remains unclear. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improve functional recovery after traumatic brain injury (TBI). But whether it inhibits white matter injury post-SCI is still unknown. Here, our results indicated that ferroptosis played an important role in the secondary white matter injury following SCI and ferrostatin-1 could reduce iron and reactive oxygen species (ROS) accumulation, downregulate the ferroptosis-related genes and its products of IREB2 and PTGS2 to further inhibit ferroptosis in oligodendrocyte progenitor cells (OPCs), finally reducing white matter injury and promoting functional recovery following SCI in rats, which enlarges the therapeutic scope for ferrostatin-1 and deciphers the potential mechanism of white matter damage after SCI.