Effects Of Puerarin On NMDAR And Learning And Memory In Rats Following Hypoxic-Ischemic Brain Damage

Objective:To investigate the effects of puerarin on expressions of N-methyl-D-aspartate(NMDA) receptor subunit NR2A and NR2B in the hippocampal CA1 region after hypoxia-ischemia brain damage(HIBD), in order to determine the protective effects of puerarin and provide the experimental basis for clinical application of HIBD.Methods:1. Establishment of HIBD model: Neonatal 7-day-old S-D rats were randomly assigned to three groups (n=10): Sham group, Con group, and Puerarin(Pue) group. The model of HIBD was performed in the method reported by Rice and Vannucci in neonatal rats from the Con and Pue groups. The Pue group received an injection of puerarin(50mg/kg) at 5 minutes after HIBD peritoneally. The rats of the Con group were given an injection of normal saline at the same dosage, once a day for 14 days. The rats of the Sham group only had their left common carotid artery freed but not ligated.2. Expressions of NR2A and NR2B: NR2A and NR2B protein expressions in the hippocampal CA1 region were detected by the immunohistochemical method at 2 w, 3 w, and 7 w after HIBD.3. Behavior tests: The capacity of learning and memory was tested on all rats with Morris water maze at 7 weeks after HIBD.Results:1. The expression levels of NR2A and NR2B in the hippocampal CA1 region in the Con group were less than those in the Sham-operated rats at any time points (P < 0.01). These levels of NR2A were significantly increased in the Pue group at 2 w and 7 w after HIBD, compared with the Con group (P < 0.05). These levels of NR2B were significantly increased in the Pue group at 2 w and 3 w after HIBD, compared with the Con group (P < 0.05).2. The average time of escape latency was significantly longer and the number of platform location crossing was less in Con group than these in Sham group (P < 0.05, P < 0.01). Compared with Con group, the average time of escape latency was significantly shorter (P < 0.05) and the number of platform location crossing was more (P < 0.05) in Pue group.Conclusion:1. The expression of NR2A and NR2B in the hippocampal CA1 region has been decrease from 2 w to 7 w after HIBD.2. There is down-regulation of the expressions of NR2A and NR2B in the hippocampal CA1 region of rats after hypoxia-ischemic brain damage, and the analytes were irretrievable. 3. Puerarin can improve permanently the learning and memory in rats with HIBD.4. The protection of puerarin on improving the learning and memory in rats with HIBD may be associated with the increased NR2A and NR2B in the CA1 region of the hippocampus from 2 w to 7 w after HIBD.