ORC ID , Hao Qiao1, Dong-Fan Liu1, Jie Li1, Jia-Xi Li1, Su-E Chang1, Teng Lu1, Feng-Tao Li1, Dong Wang1, Hao-Peng Li1, Xi-Jing He PhD, MD 2 ORC ID , Fang Wang1 ORC ID ">
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RESEARCH ARTICLE
Year : 2022  |  Volume : 17  |  Issue : 6  |  Page : 1324-1333

Lithium promotes recovery after spinal cord injury


1 Department of Orthopedics, The Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, China
2 Department of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine; Department of Orthopedics, Xi’an International Medical Center Hospital, Xi’an, Shaanxi Province, China

Correspondence Address:
Fang Wang
Department of Orthopedics, The Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province
China
Xi-Jing He
Department of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine; Department of Orthopedics, Xi’an International Medical Center Hospital, Xi’an, Shaanxi Province
China
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Source of Support: This work was supported by the National Natural Science Foundation of China, Nos. 81701223 (to FW), 81601081 (to SEC); and the Natural Science Foundation of Shaanxi Province of China, Nos. 2017JQ8019, 2021JM-290 (both to FW), Conflict of Interest: None


DOI: 10.4103/1673-5374.327348

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Lithium is associated with oxidative stress and apoptosis, but the mechanism by which lithium protects against spinal cord injury remains poorly understood. In this study, we found that intraperitoneal administration of lithium chloride (LiCl) in a rat model of spinal cord injury alleviated pathological spinal cord injury and inhibited expression of tumor necrosis factor α, interleukin-6, and interleukin 1 β. Lithium inhibited pyroptosis and reduced inflammation by inhibiting Caspase-1 expression, reducing the oxidative stress response, and inhibiting activation of the Nod-like receptor protein 3 inflammasome. We also investigated the neuroprotective effects of lithium intervention on oxygen/glucose-deprived PC12 cells. We found that lithium reduced inflammation, oxidative damage, apoptosis, and necrosis and up-regulated nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 in PC12 cells. All-trans retinoic acid, an Nrf2 inhibitor, reversed the effects of lithium. These results suggest that lithium exerts anti-inflammatory, anti-oxidant, and anti-pyroptotic effects through the Nrf2/heme oxygenase-1 pathway to promote recovery after spinal cord injury. This study was approved by the Animal Ethics Committee of Xi’an Jiaotong University (approval No. 2018-2053) on October 23, 2018.


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