Transient receptor potential melastatin 2 (TRPM2) is an important ion channel that represents a potential target for treating injury caused by cerebral ischemia. However,it is unclear whether reducing TRPM2 expression can help repair cerebral injury,and if so what the mech-anism underlying this process involves. This study investigated the protective effect of reducing TRPM2 expression on pheochromocytoma (PC12) cells injured by oxygen-glucose deprivation (OGD). PC12 cells were transfected with plasmid encoding TRPM2 shRNAS,then subjected to OGD by incubation in glucose-free medium under hypoxic conditions for 8 hours,after which the cells were allowed to reox-ygenate for 24 hours. Apoptotic cells,mitochondrial membrane potentials,reactive oxygen species levels,and cellular calcium levels were detected using flow cytometry. The relative expression of C-X-C motif chemokine ligand 2 (CXCL2),NACHT,LRR,and PYD domain–containing protein 3 (NALP3),and caspase-1 were detected using fluorescence-based quantitative reverse transcription-polymerase chain reaction and west blotting. The rates of apoptosis,mitochondrial membrane potentials,reactive oxygen species levels,and cellular cal-cium levels in the TRPM2-shRNA + OGD group were lower than those observed in the OGD group. Taken together,these results suggest that TRPM2 knockdown reduces OGD-induced neuronal injury,potentially by inhibiting apoptosis and reducing oxidative stress levels,mitochondrial membrane potentials,intracellular calcium concentrations,and NLRP3 inflammasome activation.