Dexamethasone Exacerbates Learning Deficits After Traumatic Brain Injury In Rats

Objective:To observe the changes of spatial learning ability in rats which were received different doses of DXM treatment after fluid percussion injury.Provide experimental foundation of rational treatment for using DXM after traumatic brain injury.Methods:The experiment uses adult male Wistar rats(n=156) which were randomly divided into six different groups,including naive group(n=18),sham group(n=18), injury control group(n=30),saline treatment group(n=28),moderate-dose DXM treatment group(n=30) and high-dose DXM treatment group(n=32).We use MODEL01-B hydraulic impact instrument to make TBI models in reference to stereotaxic coordinates of rat brain.After fluid percussion injury,rats were received different treatments according to the group.Rats were subjected to receiving DXM(5 mg/kg for moderate-dose and 10 mg/kg for high-dose) for treatment,and rats in saline treatment group were received equal-dose sterile saline instead.We observed brain injury condition in rats through NSS and MR imaging.Brain sections were also examined by HE,Golgi impregnation and TUNEL staining to investigate the morphological changes and apoptosis of hippocampal pyramidal neurons.We evaluated changes of spatial learning ability in rats by Morris water maze place navigation test and spatial probe test.Results of the experiment was observed and analyzed statistically by SPSS 13.0.Results:Rats had definitely injured after impaction,Local contusion was formed by fluid impact which could observe in HE-staining and MRI.Histological staining revealed morphological changes of hippocampal pyramidal neurons,and these were worsened in rats given high-dose DXM.We could see apoptosis was occurred in different level among pyramidal cells in CA1 and CA3 region of hippocampus especially in High-dose DXM group by TUNEL staining.There were more TUNEL positive cells in High-dose DXM treatment group than other groups(P＜0.01) in CA1 region.NSS was significantly raised after injury,but declined in a short time and recovered obviously in 7 days.The latency and path length were significantly higher in rats after FPI toward control group(P＜0.05) in Morris water maze.Moderate and High-dose DXM groups were also higher than Control group(P＜0.05) on these two aspects.High-dose DXM group had a statistical difference with Injury control group (P＜0.05) and Saline treatment group(P＜0.05).With regard to the probe trial,the percent time in the target quadrant was significantly lowest(P＜0.05) in injured rats receiving high-dose DXM as well,but the swimming speed had no statistical difference in all groups.We also observed that the death rate in High-dose DXM group(62.5%) was much higher than Injury control group and any other groups(P＜0.05).Conclusion:These findings indicate that the administration of high-dose DXM after TBI could worsen apoptosis and morphological changes of pyramidal neurons in hippocampus and,as a result,exacerbate learning deficits.High-dose DXM could raise the mortality of TBI.