Abstract: Neuroinflammation exacerbates secondary damage after spinal cord injury, while microglia/macrophage pyroptosis is important to neuroinflammation. Circular RNAs (circRNAs) play a role in the central nervous system. However, the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied. In the present study, we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury, along with upregulated levels of circ0000381 in the spinal cord. Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p (miR-423-3p), which can increase the expression of NOD-like receptor 3 (NLRP3), a pyroptosis marker. Therefore, upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis. Indeed, 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 spinal cord injury. Accordingly, circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.

Key words: circ0000381, inflammasome, macrophage, microglia, miR-423-3p, neuroinflammation, neuroprotection, NLRP3, pyroptosis, RNA-Seq, spinal cord injury