Methyl Prednisolone Cycle In Rat Brain Protective Effect Of Deep Hypothermic

Objective:The technique of deep hypothermic circulatory arrest has been widely applied in cardiac surgery after 1950s, but the temporarily or permanent neural complications were high to 4％～25％. Therefore, it is very important to investigate the mechanism of brain scathe and how to prolong the safe time of DHCA. Recent researches find that Methylprednisolone can restrain the hydrocephalus and the inflammation after DHCA, but the detailed mechanism is not clear. In the present study, we used a new brain protection model of deep hypothermic circulatory arrest in rats to explore the influence of methylprednisolone on the expression of NMDAR1 protein and NMDAR1mRNA.Methods:PartⅠ: To establish and appraise the brain protection model of deep hypothermic circulatory arrest in rats: 30 SD rats were divided randomly into three groups: Carotid occlusion DHCA group; inner carotid shunt DHCA group and Shame group. Recording the electroencephalograph (EEG) 24 hours after DHCA, then separating from DHCA and rewarming. All rats were killed 24 hours after DHCA, then measure the brain moisture content.PartⅡ: Influence of methylprednisolone on the expression of NMDAR1 after DHCA: Using wistar rat model of deep hypo-thermic circulatory arrest, 240 SD rats were divided randomly into three groups: Sham group; Methylprednisolone(MP) group and Model group. After separation from DHCA, rats were killed at 2h, 4h, 12h, 1d, 2d and 3d and 1 week, the expressions of N-methyl-D-aspartate receptor 1 protein were detected by immunohistochemistry.PartⅢ: Influence of methylprednisolone on the expression of NMDAR1 mRNA after DHCA: Using wistar rat model of deep hypothermic circulatory arrest, 144SD rats were divided randomly into three groups: Sham group(group A); Model group(group B) and Methylprednisolone (MP) group(group C). After separation from DHCA, rats were killed at 2h, 4h, 12h, 1d, 2d and 3d, the expressions of N-methyl-D-aspartate receptor 1 mRNA were detected by RT-PCR.Results:PartⅠ: Theαwave relative power of EEG in inner carotid shunt DHCA group was lower than that in Carotid occlusion DHCA group(P＜0.01), they were both lower than that in Sham group(P＜0.01); Theθwave relative power of EEG in inner carotid shunt DHCA group was lower than that in Carotid occlusion DHCA group and Sham group(P＜0.01), and there was no difference between Carotid occlusion DHCA group and Sham group. The brain moisture content was higher in inner carotid shunt DHCA group than Carotid occlusion DHCA group(P＜0.01).PartⅡ: Hydrocephalus can be observed at 6h after separation from DHCA, reached peak at 24h, and gradually come back to normal level at 3d in MP group and Model group. In contrast to the Model group, hydrocephalus reduced significantly in MP group(P＜0.01). The expressions of N-methyl-D-aspartate receptor 1 protein was increased at 2h after separa-tion from DHCA, reached peak at 24h, and gradually come back to normal level at 7d in MP group and Model group. However, Preconditioning with Methylprednisolone re-sulted in a significant reduction in the expressions of NMDAR1 at 2h, 6h, 12h, 1d and 2d after separation from DHCA comparing with Model group(P＜0.05).PartⅢ: The expressions of N-methyl-D-aspartate receptor 1 mRNA were on basal level in Sham group and the expressions of NMDAR1 mRNA were significantly higher in Model group than MP treatment group(P＜0.01).Conclusion:(1) Inner carotid shunt DHCA group is a more perfect brain protection model of DHCA.(2) Preconditioning with Methylprednisolone inhibits the expression of N-methyl-D-aspartate receptor 1 protein after DHCA in rats. This maybe a important mechanism of cerebral protection of preconditioning with Methylprednisolone.(3) Methylprednisolone maybe decrease the expression of NMDAR1 mRNA. This maybe a important mechanism of cerebral protection of preconditioning with Methylprednisolone.