Effects Of Memantine On NR2A Expression Following Focal Cerebral Ischemia-reperfusion In Mice

Objective: To explore the neuro-protective mechanism of memantine by studying theNR2A expression following focal cerebral ischemia-reperfusion in mice.Methods: Ninety-six adult male Kun Ming mice were randomly assigned intosham-operated group, control group and memantine-intervention group.The middlecerebral artery (MCA) of mice in the latter2groups was occluded for2hours usingintra-luminal suture method and then reperfused for22hours by withdrawing thesuture. The infarction volume was determined with TTC staining.Cerebral edemaformation was determined by brain water content．Nitrale reductase method wasperformed to detect the NO concentration. HE staining was for morphologicallydescription. The neurons of structural integrity in hippocampus CA1zone werecalculated after Nissl’s staining. Expression of NR2A in neurons of hippocampusCA1zone was determined by IHC staining.Results: The TTC staining of sham group shows no damage, while the percentage ofinfarct volume in control group and memantine group were34.23%±3.76%and28.38%±2.25%（P﹤0.05）. Memantine significantly decreased brain water contentfrom82.83％±0.72％to80.20％±0.77％. The NO concentration of telencephalons inipsilateral hemispheres of surgery in three groups were1.281±0.049umol/g,3.126±0.381umol/g and2.087±0.384umol/g, and the differences in three groups andbetween any two groups are significant（P﹤0.05）.HE staining shows loosendhistological structure and fewer neurons in ipsilateral hemisphere of MCAO.Inhippocampus CA1area, the number of neurons of structural integrity in every highpower lense by Nissl’s staining and the IOD of NR2A by IHC staining in controlgroup decreased to18.6±2.3and3879.24±259.13repectively,compared with33.0±3.8and6773.89±347.18in sham group, and memantine increased these to24.7±2.4and4482.22±310.55significantly（P﹤0.05）. In sham group, IHC showedNR2A staining mainly in cell membrane and cytoplasm,while there are more nuclear-stained neurons in ipsilateral hemisphere of MCAO.Conclusion:The down-regulation of NR2A which is mainly situated in synapsesafter Focal cerebral ischemia-reperfusion may contribute to the ischemic lesion.Memantine could up-regulate the expression of NR2A by inhibiting the activities ofextrasynaptic NMDAR and calpain, and hence exhibits neuro-protective effect.