RESUMO
Objective To investigate the relationship between the plasticity of dendritic spines in entorhinal cortical neurons and mechanism of low-dose ketamine-induced reduction of cognitive dysfunction following sevoflurane anesthesia in aged rats.Methods Thirty-six pathogen-free healthy male SpragueDawley rats,aged 18 months,weighing 500-600 g,were divided into 3 groups (n=12 each) using a random number table:control group (group C),sevoflurane anesthesia group (group Sev) and ketamine group (group K).Group C received no treatment.Group Sev inhaled the mixture of air (flow rate 1 L/min) and 3.6％ sevoflurane for 3 h.In group K,ketamine 10 mg/kg was injected intraperitoneally,and 5 min later the mixture of air (flow rate 1 L/min) and 3.6％ sevoflurane was inhaled for 3 h.Open field test and Morris water maze test were performed 3 days after anesthesia.After the behavioral tests,the animals were sacrificed,and their brains were removed and cut into sections for determination of the density of neurons,density of dendritic spines,and expression of postsynaptic density protein-95 (PSD-95) and synaptophysin (SY38) in superficial laminaes (Ⅱ-Ⅲ) of entorhinal cortex using Nissl's staining,Golgi staining and immunohistochemistry,respectively.Results Compared with group C,the time of staying at the central region was significantly shortened,the escape latency was prolonged,the density of dendritic spines was decreased,and the expression of PSD-95 and SY38 was down-regulated in group Sev (P＜0.05).Compared with group Sev,the time of staying at the central region was significantly prolonged,the escape latency was shortened,the density of dendritic spines was increased,and the expression of PSD-95 and SY38 was upregulated in group K (P＜0.05).There were no significant differences in the density of neurons in entorhinal cortex between the three groups (P＞0.05).Conclusion The mechanism by which low-dose ketamine attenuates cognitive dysfunction induced by sevoflurane anesthesia may be related to the enhanced plasticity of dendritic spines in entorhinal cortical neurons of aged rats.