Oxycodone suppresses the apoptosis of hippocampal neurons induced by oxygen-glucose deprivation/recovery through caspase-dependent and caspase-independent pathways via κ- and δ-opioid receptors in rats.

Cerebral ischemia/reperfusion injury (CIRI) can lead to perioperative neurocognitive disorders (PND) during clinical recanalization procedures in cerebral vessels, principally due to neuronal apoptosis in the hippocampus. Oxycodone appears to be a multiple opioid receptor agonist and exerts intrinsic antinociception activity via κ-opioid receptor (KOR). Recent evidence has revealed that activation of both δ-opioid receptor (DOR) and KOR can provide neuroprotection against CIRI in vivo and in vitro. In our study, we established an oxygen-glucose deprivation/recovery (OGD/R) model with fetal hippocampal neurons and found that oxycodone could induce CIRI tolerance in these neurons, primarily through KOR and DOR. Possible mechanisms might involve the regulatory effect of oxycodone on the MAPK-Bcl2/Bax-caspase-9-caspase-3 pathway, as well as its inhibitory effect on cellular reactive oxygen species (ROS) production and mitochondrial membrane potential activation. Taken together, our findings may indicate a potential method for the prevention and treatment of PND associated with CIRI.