Dexmedetomidine provides protection to neurons against OGD/R-induced oxidative stress and neuronal apoptosis

Dexmedetomidine, a potent α2-adrenoceptor (α2-AR) agonist, is extensively used in the operating room (OR) and intensive care unit (ICU) and has been applied for the treatment of several diseases. Western blotting has been routinely used to investigate the protein levels of α-adrenergic receptor (α-AR), apoptosis related proteins (Bcl-2, Bax and Cleaved Caspase 3) and a range of proteins associated with the Nrf2/ARE pathway (Nrf2, HO-1, NQO-1, SOD) in neurons. The CCK-8 assay was used to determine cell survival rates while the Co-IP assay was used to investigate the binding ability between α2-AR and Nrf2. The TUNEL assay was used to detect cell apoptosis in neurons. OGD/R treatment reduced the level of α2-AR protein in neurons and reduced neuronal survival in a time-dependent manner. However, treatment with dexmedetomidine led to the increased protein expression of α2-AR in OGD/R-treated neurons and enhanced survival rate of OGD/R-treated neurons. From a mechanistic point-of-view, Nrf2 can effectively bind with α2-AR. Silencing Nrf2 reversed the effects of dexmedetomidine on cell viability, oxidative stress, and neuronal apoptosis in OGD/R-treated neurons. The activation of α2-AR by dexmedetomidine had a protective effect in neurons against OGD/R-triggered oxidative stress and neuronal apoptosis by modulating the Nrf2/ARE pathway.