Effect of acupuncture on pyroptosis pathways after spinal cord injury

Spinal cord injury (SCI) triggers caspase-dependent pyroptosis, amplifying neuroinflammation and secondary damage. Electroacupuncture (EA), a clinically validated rehabilitative intervention, mitigates SCI by targeting pyroptosis-specific mechanisms. Mechanistically, EA inhibits NLRP3 inflammasome assembly and reduces ASC speck formation, thereby suppressing caspase-1 activation. This attenuates gasdermin D (GSDMD) cleavage, pore formation, and IL-1β/IL-18 maturation in microglia and macrophages. Furthermore, EA downregulates cytidine monophosphate kinase 2 (CMPK2) and upregulates calcitonin gene-related peptide (CGRP), disrupting pyroptotic signaling. Evidence from rodent models confirms that EA at spinal Jiaji (EX-B2) or Du meridian acupoints modulates microglial activation and NLRP3/GSDMD-N expression, reducing neuronal pyroptosis and improving motor recovery. While EA demonstrates therapeutic promise via pyroptosis regulation, further mechanistic studies are warranted to define its interactions with non-canonical pathways (e.g., caspase-4/5/11). This review synthesizes current evidence and identifies molecular targets for optimizing EA-based neuroprotection post-SCI. • Examines EA's potential in treating SCI by regulating pyroptosis. • Review extensive literature to provide an comprehensive research background. • Assess EA efficacy for SCI recovery by integrating preclinical and clinical data. • Analyze challenges in clinical translation of EA and propose solutions.