Dexmedetomidine Possesses Neuroprotective Effects during Ischemic Stroke by Activating the AKT/mTOR Pathway.

Abstract

Dexmedetomidine (DEX) exerts neuroprotective effects following ischemic stroke (IS) by regulating several pathways, such as extracellular signal-regulated kinase 1 and 2 pathway and Ca2⁺-stromal interaction molecule 1/Orai calcium release-activated calcium channel protein 1 pathway, according to previous studies. However, the underlying mechanisms are not entirely elucidated yet. The purpose of this study was to investigate the impact of DEX on inhibiting neuron damage during IS, and the potential mechanism. Hippocampal neurons (HT22 cells) were treated with oxygen-glucose deprivation/reoxygenation (OGD/R) in the presence of 1 _μM DEX, 10 _μM LY294002 [a protein kinase B (AKT) inhibitor], or their combination. DEX increased viability and reduced apoptosis in OGD/R-stimulated hippocampal neurons. DEX reduced lactate dehydrogenase (LDH) and reactive oxygen species (ROS), but increased superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) in OGD/R-stimulated hippocampal neurons. These discoveries indicated that DEX mitigated OGD/R-triggered oxidative stress in hippocampal neurons. DEX increased phosphorylated-AKT/AKT and phosphorylated-mammalian target of rapamycin (mTOR)/mTOR in OGD/R-stimulated hippocampal neurons, which suggested that DEX activated the AKT/mTOR pathway. LY294002 inhibited the AKT/mTOR pathway and viability, but enhanced apoptosis and oxidative stress in OGD/R-stimulated hippocampal neurons. Notably, LY294002 reversed the effect of DEX on the above-mentioned processes in OGD/R-stimulated hippocampal neurons. In conclusion, DEX inhibits OGD/R-triggered hippocampal neuron injury by activating the AKT/mTOR pathway, which is conducive to attenuating IS progression.