| Background: Following surgery, elderly patients often suffer from postoperative cognitive dysfunction(POCD), which is one of the complications in central nervous system(CNS) postoperatively . At present the pathogenesis of POCD has not been clear, but some reports have shown that aging and surgical stress are the two major risk factors for POCD. It has been considered that POCD was related to central inflammation reaction after surgery as the central nervous system is going degenerative in elderly patients. Microglial activity will be increased after surgery and anesthesia , then lots of inflammatory molecules, such as IL-1β,will be released significantly. The neuron cells and cognition function will be damaged by the high levels of IL-1β.GSK-3βplays an important role in regulating central inflammation reaction and memory. It is reported that GSK-3βpromoted both microglial migration and inflammatory molecules release so that induced neurotoxicity. GSK-3βactivity also is the key target for control of the tau protein hyperphosphorylation and Aβincrease in Alzheimer's disease. Lithium plays an important role in anti-neurodegeneration. It is reported that lithium could reduce neurons apoptosis and promote neurons regeneration, also reduce the phosphorylation level of tau protein to improve cognitive function in Alzheimer's rats. Its mechanism is related to anti-inflammation Objective: To observe the change of spatial memory, IL-1βexpression and GSK-3βactivity in aged rats'hippocampuses after exploratory laparotomy, and explore the effect of lithium pretreatment to these changes.Methods: Forty-eight male Sprague-Dawleyspell(SD) rats, aged 18 month, were randomly divided into three groups (n=16 in each group): control (C), operation (O) and lithium chloride group (L). The rats in group L were injected with 2 mEq/kg lithium chloride (i.p.) once a day for seven days, while the rats in other two groups were injected (i.p.) with the same volume of normal saline. All rats except group C underwent exploratory laparotomy on eighth day under 2% pentobarbital sodium anesthesia. Twenty four hours after surgery, the rat's spatial memory(8 rats of each group) was evaluated by Morris Water Maze for 3 days, The others rats were execute 24h after surgery, then the contents of IL-1βor GSK-3βin rats'hippocampuses were measured by ELISA or western blotting.Results: The latency and swimming distance on 2nd day of group L and C were both significantly shorter then that of 1st day (p<0.05). The latency and swimming distance on 3rd day of group L and C were both significantly shorter then that of 1st and 2nd days (p<0.05). the swimming distance on 1st day of group L was significantly prolonged than group C (p<0.05).The latency and swimming distance were both significantly prolonged postoperatively in group O compared with group C on three days(p<0.05). The swimming distance of group O on 2nd and 3rd were significantly longer than group L(p<0.05).The latency and swimming distance on 3rd day of group O were both significantly shorter then that of 1st day (p<0.05). In addition, IL-1βexpression increased while phospho-GSK-3β(ser9) decreased in hippocampus in group O vs. group C (P<0.05) but lithium treatment reversed these changes (p<0.05, respectively). The differences of GSK-3βexpression were not significant among three groups postoperatively (P>0.05).Conclusions: Spatial memory function is impaired significantly after exploratory laparotomy in aged rats, which is associated with the increase of IL-1βand the decrease of phospho-GSK-3β(ser9) in hippocampus. However, lithium pretreatment could reverse these changes markedly, indicating that lithium has potential beneficial effects on spatial memory through reducing central inflammation reaction and phosphorylating GSK-3βin aged rats undergoing surgery.
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