The role of NMDA receptor subunit 2A in ischemia/reperfusion injury of rat hippocampus

Objective To observe the changes of NMDA receptor subunit 2A (NR2A) expression in rat hippocampal CA1 subfield during ischemia/reperfusion following blockage by NR2A-specific antisense oligonucleotide,and to further reveal the role of NR2A in ischemic brain injury.Methods Healthy male SD rats were randomized into normal control group,sham operation control group and ischemia/reperfusion group.After respective pretreatment with antisense oligonucleotide,sense oligonucleotide,saline and blank control,the four-vessel occlusion method was adopted to establish animal model of transient forebrain ischemia (15 min) and reperfusion (24 h and 48 h) .Within the determined time,the rats were sacrificed for paraffin-embedded tissue sections (slice thickness of 8 μm) .The slices were processed by in situ hybridization staining,TUNEL staining and Cresyl violet staining.Results In the early period of ischemia /reperfusion (24 h) ,the expression of NR2A mRNA in CA1 subfield of rat hippocampus significantly increased (P 0.05) .Following pretreatment with antisense oligonucleotide,the expression of NR2A mRNA in CA1 subfield of rat hippocampus significantly decreased (P 0.05) .Meanwhile,TUNEL staining also showed that the number of apoptotic cells significantly decreased at the time points as 24 h and 48 h of ischemia-reperfusion (P 0.05) .Conclusion After transient forebrain ischemia,the expression level of NR2A mRNA was consistent with the apoptosis in time and space,suggesting that NR2A might be involved in the process of apoptosis induced by cerebral ischemia and reperfusion.