Docosahexaenoic acid supplementation alleviates behavioral memory impairment caused via repeated administration of sevoflurane in aged rats

Elderly patients often need repeated surgical intervention, so it is important to determine the impact of repeated exposure to anesthetics on learning and memory. Docosahexaenoic acid (DHA) is considered to be an essential nutrient for maintaining brain health. The aim of the present study was to explore the potential effects of DHA on memory impairment induced by repeated sevoflurane anesthesia in aged rats. A total of 54 Sprague Dawley aged rats (18 months) were randomly divided into the following six groups: i) Control group; ii) sevoflurane group (Sev, 2.5% for 5 min); iii) DHA group (3 g/kg); iv) Sev + DHA (0.3 g/kg) group; v) Sev + DHA (1 g/kg) group; and vi) Sev + DHA (3 g/kg) group. Morris water maze experiment was performed to evaluate the learning and memory ability of the rats following treatment. H&E staining was used to observe any histological changes. Superoxide dismutase, malondialdehyde and glutathione peroxidase levels were detected using ELISA. Immunohistochemistry and western blotting were used to determine nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein expression levels. Following repeated sevoflurane anesthesia, rats exhibited a prolonged escape latency. The number of times rats crossed the platform and the time spent in the target quadrant were also significantly reduced by repeated sevoflurane anesthesia. However, rats treated with Sev + DHA exhibited a reduced escape latency, whilst the number of times they crossed the platform and the time spent in the target quadrant increased compared with Sev treatment alone. Histopathological examination revealed that DHA treatment ameliorated the disordered neuron arrangement, deep staining of the neuronal nucleus pyknosis and cell edema observed in the brain tissue induced by repeated sevoflurane anesthesia. Furthermore, the protein expression levels of Nrf2 and HO-1 were demonstrated to be significantly increased in rats treated with DHA and exposed to repeated sevoflurane anesthesia compared with those in untreated rats that underwent repeated sevoflurane anesthesia. In conclusion, the present study revealed that DHA exerted protective effects against impairments in learning and memory induced by repeated sevoflurane anesthesia in aged rats, which may be associated with the Nrf2/HO-1 signaling pathway.