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Updated: Sep 10, 2025
Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice
Published on: July 16, 2015
Spinal cord ischemia reperfusion injury induces cuproptosis in neurons
Lei Xie1,2, Hang Wu2,3, Qiuping He1,2
1Department of Orthopedic Surgery, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Background:
Spinal cord ischemia reperfusion injury (SCIRI) is a serious disease that can result in irreversible neuronal damage, leading to the loss of sensory and motor function. Cuproptosis, a novel form of regulated cell death, has been studied in various diseases. However, the role and mechanism of cuproptosis in SCIRI remain to be elucidated.
Results:
The results of transcriptome analysis showed significant downregulation of ATP7B, which regulates copper ion efflux. Concurrently, another key cuproptosis-related gene, FDX1, was significantly altered. Thus, we performed qPCR and Western blot assays in vivo and in vitro to detect changes in cuproptosis-related genes. The results indicated that cuproptosis was indeed activated by SCIRI or OGD/R. Moreover, immunofluorescence/immunohistochemitry staining and neuronal activity tests were consistent with the above results. Furthermore, we also proved that ammonium tetrathiomolybdate, a copper chelator and cuproptosis inhibitor, could not only ameliorate neuronal damage and promote neuronal survival but also improve lower limb motor dysfunction.
Conclusions:
SCIRI caused ATP7B downregulation, which blocked copper ion efflux, leading to copper ion accumulation, DLAT oligomerization, degradation of iron-sulfur cluster proteins and ultimately cuproptosis in neurons.
