Relationship between hippocampal N - methyl - D - aspartate receptor and cognitive impairment of vascular dementia rat model

doi:10.3321/j.issn:1673-8225.2003.10.008

Abstract：Aim By establishing a reliable vascular dementia (VD) rat model to study the changes of the N - methyl - D - aspartate receptor1 (NMDAR) mRNA expression in rat's hippocampus, and to provide the theoretical basis for the mechanism of NMDAR's effect on cognitive impairment of VD rat model.Methods The VD rat model was established by improved Pulsinelli's four - vessel occlusion(4VO) method.The changes of memory ability, long - term potentiation (LTP) in CA1 area and the NMDAR1mRNA expression in the hippocampus were examined by computerized shuttle - training case, extracorporeal hippocampal slices method and in situ hybridization. Results Compared with the control group,the (active avoidance response,AAR) in the VD model group was less in the 2nd week,the 4th week and the 2nd month(P< 0.05).It was more obviously at the later two time points (P< 0.01).In the slices of extracorporeal hippocampal CA1 region,LTP detection showed that its injury had happened clearly in VD model group at each time point of the 2nd week, the 4th week and the 2nd month.Compared with the control group, at the 2nd week the mean optical density(OD) of NMDAR1mRNA expression in pyramidal cell layer of hippocampus in the VD model group was increased in the CA1 and CA3 regions,but no changes were found in DG region;at the 4th week and the 2nd month,it was decreased in each region.Conclusion The hippocampal NMDA receptor is related to the cognitive impairment of VD rat model.In the early phase of the brain ischemic - reperfusion injury,the expression of NMDAR mRNA increases,which mediate the exitotoxicity, but it decreases in the anaphase,which might be correlated to the learning and memory impairment of VD.Therefore it supplies the foundation to use antagonist or agonist of EAAs receptor in the VD therapy.