Neuroprotective role of delta opioid receptors in hypoxic preconditioning

Abstract

Background/aim: The purpose of the present study was to explore the neuroprotective role of delta opioid receptors (DOR) in the ratcortex in hypoxic preconditioning.Materials and methods: Rats were randomly divided into 8 groups: control (C), sham (S), hypoxic preconditioning (PC), severe hypoxia(SH), PC + SH, PC + SH + Saline (PS), PC + SH + DPDPE (DPDPE, selective DOR agonist), PC + SH + NT (NT, Naltrindole, selectiveDOR antagonist). Drugs were administered intracerebroventrically. Twenty four h after the end of 3 consecutive days of PC (10% O2,2 h/day), the rats were subjected to severe hypoxia (7% O2 for 3 h). Bcl-2 and cyt-c were measured by western blot, and caspase-3 wasobserved immunohistochemically.Results: Bcl-2 expressions in the PC group were higher than in control, SH, and PC + SH groups. Even though there were no significantdifferences between the groups in terms of cyt-c levels, caspase-3 immunoreactivity of cortical neurons and glial cells in the severehypoxia and NT groups were higher than in the control, sham, and hypoxic preconditioning groups. DPDPE administration diminishedcaspase-3 immunoreactivity compared with all of the severe hypoxia groups.Conclusions: These results suggest that cortical cells are resistant to apoptosis via increased expression of Bcl-2 and decreasedimmunoreactivity of caspase-3 in the cortex, and that DOR is involved in neuroprotection induced by hypoxic preconditioning via thecaspase-3 pathway in cortical neurons.