Abstract
Spinal cord injury (SCI), a devastating neurological impairment, usually imposes a long-term psychological stress and high socioeconomic burden for the sufferers and their family. Recent researchers have paid arousing attention to white matter injury and the underlying mechanism following SCI. Ferroptosis has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improving functional recovery after traumatic brain injury (TBI) and SCI. However, the role of ferroptosis in white matter injury and the therapeutic effect of ferrostatin-1 on SCI are still unknown. Here, our results indicated that ferroptosis played a pivotal role in the secondary white matter injury, and ferrostatin-1 could reduce iron and reactive oxygen species (ROS) accumulation and downregulate the ferroptosis-related genes and its products of IREB2 and PTGS2 to further inhibit ferroptosis in oligodendrocyte, finally reducing white matter injury and promoting functional recovery following SCI in rats. Meanwhile, the results demonstrated that ferrostatin-1 held the potential of inhibiting the activation of reactive astrocyte and microglia. Mechanically, the present study deciphers the potential mechanism of white matter damage, which enlarges the therapeutic effects of ferrostatin-1 on SCI and even in other central nervous system (CNS) diseases existing ferroptosis.
Highlights
Spinal cord injury (SCI), a devastating neurological impairment, usually occurs in subpopulation with workforce, and imposes a long-term psychological stress and high socioeconomic burden for the suffers, as well as their family [1,2,3]
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), 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
Our past studies have uncovered a variety of therapeutic candidates associated with secondary injury, including promoting neuron survival through inhibiting acid-sensing ion channel 1a (ASIC 1a) [4] or activating G-protein coupled estrogen receptor 1 (GPER1) [2,5], mediating neuroinflammation by complement C5a [6], decreasing glial scar formation and potentiating axon regeneration using curcumin, antisense vimentin cDNA combined with chondroitinase ABC [7,8,9], and cell-based strategies using exogenous transplantation of human umbilical cord mesenchymal stem cells [10] and directing endogenous neural stem cells (NSCs) differentiation into neurons [11,12]
Summary
Spinal cord injury (SCI), a devastating neurological impairment, usually occurs in subpopulation with workforce, and imposes a long-term psychological stress and high socioeconomic burden for the suffers, as well as their family [1,2,3]. Our past studies have uncovered a variety of therapeutic candidates associated with secondary injury, including promoting neuron survival through inhibiting acid-sensing ion channel 1a (ASIC 1a) [4] or activating G-protein coupled estrogen receptor 1 (GPER1) [2,5], mediating neuroinflammation by complement C5a [6], decreasing glial scar formation and potentiating axon regeneration using curcumin, antisense vimentin cDNA combined with chondroitinase ABC [7,8,9], and cell-based strategies using exogenous transplantation of human umbilical cord mesenchymal stem cells [10] and directing endogenous neural stem cells (NSCs) differentiation into neurons [11,12]. Evidence have shown that the limited number of epibiotic axons holds sufficient potential in facilitating locomotor function recovery post-SCI [13,14,15], suggesting that promoting remyelination during the acute phase might be a feasible strategy for SCI treatment. Investigation presents that Liproxstatin-1 (Lipro-1), an inhibitor of ferroptosis, protects oligodendrocytes from ferroptosis through inhibiting lipid peroxidation and increasing expression of glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferroptosis suppressor protein 1 (FSP1) [19]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
