Dexmedetomidine protects against oxygen–glucose deprivation-induced injury through the I2 imidazoline receptor-PI3K/AKT pathway in rat C6 glioma cells

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>To explore the protection and the mechanism of dexmedetomidine on the oxygen–glucose deprivation (OGD) insults in rat C6 glioma cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Cells were subjected to OGD then assessed by viability studies. After dexmedetomidine treatment, p-AKT, hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF) and RTP801 expression were measured.</jats:p> </jats:sec> <jats:sec> <jats:title>Key findings</jats:title> <jats:p>Three hours of OGD decreased cell viability to 48.8%, which was reversed to 67.4% by 1 µm dexmedetomidine. Hoechst 33342 and propidium iodide double stains showed that the protection of dexmedetomidine was mainly by an anti-apoptosis effect, which was also strengthened by decreasing caspase-3 expression. Dexmedetomidine protection was mainly blocked by the I2 imidazoline receptor antagonist idazoxan and BU 224, but not by the α1-adrenoceptor antagonist prazosin, the α2-adrenoceptor antagonist yohimbine and RX 821002, or the I1 imidazoline receptor antagonist efaroxan. On the other hand, dexmedetomidine enhanced AKT phosphorylation. Furthermore, the protection of dexmedetomidine was blocked by the PI3K/AKT inhibitor wortmannin. The proteins of HIF-1α, VEGF and RTP801 were significantly increased by dexmedetomidine treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Dexmedetomidine activated the I2 imidazoline receptor-PI3K/AKT pathway, and up-regulated HIF-1α, VEGF and RTP801 expression to protect against OGD-induced injury in rat C6 cells.</jats:p> </jats:sec>