Argon inhibits autophagy and improves cerebral ischemia-reperfusion injury via PI3K/Akt/mTOR pathway

It has been reported that argon has neuroprotective effects during cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism is not fully understood. The aim of this study is to investigate if argon could regulate autophagy to exert a neuroprotective function. A temporary middle cerebral artery ischemia mouse model (tMCAO, ischemia 3h, reperfusion 1h) and the HT22 cell line Oxygen glucose deprivation reperfusion (OGDR) model were used for argon treatment. Transcriptome sequencing and bioinformatics analysis were performed on HT22 OGDR models. Western blot, CCK-8, LDH, transmission electron microscopy, agonists and inhibitors of autophagy and PI3K/Akt/mTOR were used to investigate the specific mechanism. Argon could reduce infarct volume, improve weight recovery, and neurological scores. Enrichment analysis of the KEGG signaling pathway was highly correlated with the PI3K/Akt pathway. Western blot, CCK-8, LDH, and transmission electron microscopy showed that argon could activate the PI3K/Akt/mTOR pathway and inhibit autophagy, promoting a neuroprotective function. After the combined use of autophagy inducer 3, Akt inhibitor MK2206, and mTOR inhibitor rapamycin, respectively, the neuroprotective function of argon was significantly reversed. Our study suggests that argon activating the PI3K/Akt/mTOR pathway and inhibiting autophagy is an important mechanism for its neuroprotective function.