Fluoxetine Attenuates Memory Impairment And Cerebral Neuroinflammation Induced By Global Cerebral Ischemia In Mice

Objective: By observing the therapeutic effect of fluoxetine on memory impairment in mice with ischemic brain and its effect on interleukin 1 β(IL-1 β)and tumor necrosis factor-α(TNF-α)in cortex and hippocampus of mice to explore the therapeutic effect of fluoxetine on ischemic brain injury in mice and whether inflammatory factors are involved in its neuroprotective mechanism,so as to provide evidence for the pathophysiological mechanism and treatment of ischemic brain injury.Methods: 4-5-week-old male ICR mic mice weighting 28-30 g were randomly divided into three groups with 10 mice in each group.The mice were group-housed and maintained on a 12:12 hour light/dark cycle,with food and water freely available,for a 7-day acclimation to laboratory conditions before the experiment.The ischemia model of mice was established by bilateral common carotid artery surgery(BCCAO)and injected intraperitoneally with 10mg/kg/d fluoxetine or saline.The following three groups were produced: saline + sham surgery(Sham),saline +BCCAO surgery(BCCAO)and fluoxetine+BCCAO(FLX+BCCAO).Water maze test and Y maze test were used to detect the improvement of neurological function in mice with ischemic brain injury.Detection the levels of IL-1 β and TNF-α in cortex and hippocampus of mice by enzyme-linked immunosorbent assay(Elisa)kit.Results: ⑴In Y maze,there was no significant difference in the total times of arm entries among the three groups(P > 0.05),compared with the Sham group,the actual alternation / the maximum alternation of the BCCAO group was significantly decreased and compared with the BCCAO group,the actual alternation / the maximum alternation of the FLX+BCCAO group was significantly improved(P<0.05).⑵In Morris water maze,the training period showed that the escape latency time of BCCAO group was significantly longer than that of Sham group(P<0.05),and the escape latency time of FLX+BCCAO group was significantly shorter than that of BCCAO group(P<0.05);In the test period: compared with Sham group,the escape latency of BCCAO group was longer,the number of times of crossing the platform was decreased,and the exploration time in the target quadrant was significantly reduced(P<0.05);Compared with BCCAO group,FLX+BCCAO group had shorter escape latency,more times of crossing the platform and longer target quadrant exploration time(P<0.05);The swimming track showed that compared with BCCAO group,sham group and FLX+BCCAO group crossed the platform quadrant more purposefully and stayed longer.⑶Compared with sham group,the levels of IL-1 β and TNF-α in cortex and hippocampus of BCCAO group were significantly increased(P<0.05).Compared with BCCAO group,the expressions of IL-1 β and TNF-α in cortex and hippocampus of FLX+BCCAO group were significantly decreased(P<0.05).Conclusion: Fluoxetine has neuroprotective effect,improves learning ability and significantly reduces memory impairment in mice with ischemic brain injury,which may be achieved by inhibiting the expression of inflammatory factors IL-1 β and TNF-α.This provides a new idea for clinical treatment.