Mechanism of Cognitive Dysfunction Alleviation After Sevoflurane Anesthesia in Aged Rats Through Low-Dose Ketamine Based on the PI3K/Akt Pathway

Background and Objective: The neurotoxicity of propofol induces hippocampal neuron apoptosis, triggering cognitive dysfunction, emphasizing crucial clinical significance in preventing and treating propofol-related POCD. To explore the mechanism by which low-dose ketamine attenuates cognitive dysfunction after sevoflurane anesthesia in aged rats based on the Phosphatidylinositol 3-Kinase (PI3K)/serine-threonine Protein Kinase (Akt) pathway. Materials and Methods: Sixty aged rats were divided into control group, cognitive dysfunction group and low-dose ketamine group according to the random number table method, with 20 in each and the cognitive functions of the rats in the three groups were compared. Results: Compared with the cognitive dysfunction group, the low-dose ketamine group exhibited a lower programmed necrosis rate of hippocampus neurons and a decreased cytoplasmic Ca2+ concentration of hippocampal neurons (p<0.05). Compared with the cognitive dysfunction group, the low-dose ketamine group exhibited lower levels of IL-6, TNF-alpha, s-100 beta and NOS, while displaying higher levels of p-PI3K, p-Akt, synapsin I, synaptic proteins, synaptic vesicle proteins, dendritic spine density, neuronal density, SY38 and PSD-95 (p<0.05). Conclusion: Pre-infusion of low-dose ketamine may alleviate cognitive dysfunction after sevoflurane anesthesia in aged rats and the mechanism may be related to the inhibition of programmed necrosis of hippocampal neurons, activation of the hippocampal PI3K/Akt pathway and improvement of neuronal synaptic plasticity.