FIGURE 10.

Schematic diagram illustrating the proposed mechanism by which hypoxic preconditioned bone marrow‐derived mesenchymal stem cells (HP‐BMSCs) alleviate neuronal pyroptosis via the NLRP3 inflammasome, MAPK and NF‐κB signalling pathways following cardiopulmonary resuscitation (CPR). The expression level of HMGB1 and TLR4 was upregulated following resuscitation, including MAPK pathway activation and pyroptosis initiation. This triggered the nuclear translocation of NF‐κB and increased HMGB1 leading to NLRP3 inflammasome formation. Subsequently, NLRP3 inflammasome activation promoted the cleavage and activation of pro‐caspase‐1, which contributed to elevation in IL‐1β, IL‐18 and GSDMD‐N levels, and induced pore formation on the membrane, causing pyroptotic cell death. Hypoxic preconditioning (HP) enhanced the tolerance capacity of BMSCs to local adverse microenvironment. HP‐BMSCs inhibited HMGB1 and TLR4 activation, which decreased MAPK and NF‐κB signals, as well as preventing the formation of NLRP3 inflammasome, which in turn ameliorated neuronal pyroptosis.