CD74 Affects Ferroptosis in Traumatic Brain Injury by Modulating the Nrf2/HO‐1 Signaling Pathway

OBJECTIVE: This study aimed to explore whether CD74 participates in regulating ferroptosis and to clarify the related mechanisms in traumatic brain injury (TBI). METHODS: levels with an iron assay kit, degenerating neurons by Fluoro-Jade C staining, and Nrf2/HO-1 pathway protein expression via Western blot. RESULTS: levels, more iron-positive cells, and greater numbers of degenerating neurons in the cerebral cortex. Lip-1 or CD74 downregulation alleviated TBI-related changes, whereas RSL-3 or CD74 upregulation worsened them. Downregulating CD74 enhanced Nrf2/HO-1 pathway activity, and Nrf2 knockdown counteracted the benefits of CD74 downregulation. CONCLUSION: Reducing CD74 expression ameliorates ferroptosis in TBI by activating the Nrf2/HO-1 signaling axis.