TSPO knockdown attenuates OGD/R-induced neuroinflammation and neural apoptosis by decreasing NLRP3 inflammasome activity through PPARγ pathway.

Ischemic stroke is a cerebrovascular disease which is related to brain function loss induced by cerebral ischemia. Translocator protein (TSPO) is an important regulator in inflammatory diseases, while its role in ischemic stroke remains largely unknown. This research aimed to explore the role and action mechanism of TSPO in oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuron cell damage. The differentially expressed genes in ischemic stroke were predicted using GSE140275 dataset, DisGeNet, and GeneCards databases. Differentiated SH-SY5Y cells and primary neurons were subjected to transfection, and stimulated with OGD/R or MCC950 (NLRP3 inhibitor). Proteins were detected by western blotting and ELISA. Cell apoptosis was evaluated through CCK-8, caspase-3 activity and TUNEL assays. TSPO was upregulated in ischemic stroke and in SH-SY5Y cells and primary neurons after OGD/R treatment. TSPO silencing attenuated OGD/R-induced inflammation and apoptosis by decreasing NLRP3 inflammasome activity. TSPO downregulation increased PPARγ expression and decreased HMGB1 expression in OGD/R-treated cells, which was reversed by silencing PPARγ. PPARγ knockdown abolished the effect of TSPO silence on NLRP3 inflammasome activity, inflammation, and cell apoptosis in OGD/R-treated cells, while PPARγ overexpression alleviated OGD/R-induced injury in SH-SY5Y cells. In conclusion, TSPO knockdown attenuates neuroinflammation and neural apoptosis by decreasing NLRP3 inflammasome activity through PPARγ pathway.