Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (on line): 1-7.

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Yan Zhang1, #, Wenkai Zhang2, 3, #, Tao Liu2, Ziqian Ma2, Wenxiu Zhang1, Yun Guan4, 5, Xueming Chen1, 2, *   

  1. 1Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing, China; 2Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing, China; 3Department of Emergency Medicine, Aerospace Center Hospital, Beijing, China; 4Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 5Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Online:2023-01-01 Published:2023-07-21
  • Contact: Xueming Chen, MD, chenxueming@ccmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81901241 (to YZ).

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Abstract: Neuroinflammation exacerbates secondary damage after spinal cord injury (SCI), band microglia/macrophage pyroptosis is important to neuroinflammation. RNA sequencing (RNA-seq) analysis revealed that the expression level of circ0000381 was upregulated in the spinal cord after SCI. For examining the functional roles and the mechanisms of circular RNA 0000381 (circ0000381) in regulating microglia/macrophage pyroptosis, we established SCI model in female rats. We found that microglia/macrophage underwent pyroptosis after SCI, and the level of circ0000381 in the spinal cord was increased. Further examination unraveled that circ0000381 may function as a sponge to sequester the endogenous microRNA423-3p (miR-423-3p) which can increase the expression of NOD-like receptor 3 (NLRP3), a pyroptosis marker. Thus, the upregulation of circ0000381 may be a compensatory change after SCI to attenuate microglia/macrophage pyroptosis. Indeed, the knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis. Collectively, our findings provide novel evidence for the upregulation of circ0000381 which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after SCI. Accordingly, circ0000381 may be a novel therapeutic target for SCI treatment.

Key words: spinal cord injury, microglia, macrophage, pyroptosis, neuroinflammatory, neuroprotective, circ0000381, miR-423-3p, Inflammasome, NLRP3, RNA-seq