Aim: Spinal cord injury (SCI) involves multiple pathological processes. Ferroptosis has been shown to play a critical role in the injury process. We wanted to explore whether zinc can inhibit ferroptosis, reduce inflammation, and then exert a neuroprotective effect. Methods: The Alice method was used to establish a spinal cord injury model. The Basso Mouse Scale (BMS), Nissl staining, hematoxylin‐eosin staining, and immunofluorescence analysis were used to investigate the protective effect of zinc on neurons on spinal cord neurons and the recovery of motor function. The regulation of the nuclear factor E2/heme oxygenase‐1 (NRF2/HO‐1) pathway was assessed, the levels of essential ferroptosis proteins were measured, and the changes in mitochondria were confirmed by transmission electron microscopy and 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐imidacarbocyanine iodide (JC‐1) staining. In vitro experiments using VSC4.1 (spinal cord anterior horn motor neuroma cell line), 4‐hydroxynonenal (4HNE), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), lipid peroxides, and finally the levels of inflammatory factors were detected to assess the effect of zinc. Results: Zinc reversed behavioral and structural changes after SCI. Zinc increased the expression of NRF2/HO‐1, thereby increasing the content of glutathione peroxidase 4 (GPX4), SOD, and GHS and reducing the levels of lipid peroxides, MDA, and ROS. Zinc also rescued injured mitochondria and effectively reduced spinal cord injury and the levels of inflammatory factors, and the NRF2 inhibitor Brusatol reversed the effects of zinc. Conclusion: Zinc promoted the degradation of oxidative stress products and lipid peroxides through the NRF2/HO‐1 and GPX4 signaling pathways to inhibit ferroptosis in neurons.

Uniform, highly water-dispersible and ultra-small Fe₃O₄ nanoparticles were synthesized via a modified one-step coprecipitation approach. The prepared Fe₃O₄ nanoparticles not only show good magnetic properties, long-term stability in a biological environment, but also exhibit good biocompatibility in cell viability and hemolysis assay. Due to the ultra-small sized and highly water-dispersibility, they exhibit excellent relaxivity properties, the 1.7 nm sized Fe₃O₄ nanoparticles reveal a low r₂/r₁ ratio of 2.03 (r₁ = 8.20 mM⁻¹ s⁻¹, r₂ = 16.67 mM⁻¹ s⁻¹); and the 2.2 nm sized Fe₃O₄ nanoparticles also appear to have a low r₂/r₁ ratio of 4.65 (r₁ = 6.15 mM⁻¹ s⁻¹, r₂ = 28.62 mM⁻¹ s⁻¹). This demonstrates that the proposed ultra-small Fe₃O₄ nanoparticles have great potential as a new type of T₁ magnetic resonance imaging contrast agents. Especially, the 2.2 nm sized Fe₃O₄ nanoparticles, have a competitive r₁ value and r₂ value compared to commercial contrasting agents such as Gd-DTPA (r₁ = 4.8 mM⁻¹ s ⁻¹), and SHU-555C (r₂ = 69 mM⁻¹ s⁻¹). In vitro and in vivo imaging experiments, show that the 2.2 nm sized Fe₃O₄ nanoparticles exhibit great contrast enhancement, long-term circulation, and low toxicity, which enable these ultra-small sized Fe₃O₄ nanoparticles to be promising as T₁ and T₂ dual contrast agents in clinical settings.