Long-term activation of the glutamatergic system associated with N-methyl-D-aspartate receptors after postischemic hypothermia in gerbils

Objective: The objective of this study was to investigate whether hypotherm ia would suppress secondary damage in the chronic postischemic stage, in te rms of glutamate excitotoxicity. Methods: Gerbils underwent 5 minutes of ischemia via bilateral common carot id artery occlusion. Seven groups were studied, as follows: 1) ischemia wit hout treatment group; 2) intraischemic hypothermia group; 3) postischemic h ypothermia group (32 degreesC for 4 h); 4) MK-801 treatment group (2 mg/kg, every other day for 1 mo); 5) postischemic hypothermia with MK-801 treatme nt for I week group (2 mg/kg, every other day); 6) postischemic hypothermia with MK-801 treatment for 1 month group (2 mg/kg, every other day); and 7) sham-treated control group. One month after ischemia, histological changes in hippocampal CA1 neurons (assessed using hematoxylin and eosin staining) and memory function (assessed using an eight-arm radial maze) were studied . Extracellular glutamate concentrations were monitored by microdialysis du ring ischemia and hypothermia. Staining of microglia was performed 1 week a nd 1 month after ischemia. Results: MK-801 alone, postischemic hypothermia alone, and postischemic hyp othermia with MK-801 treatment for 1 week failed to prevent ischemic neuron al damage and memory function decreases 1 month after the insult (P<0.05 ve rsus control). However, the postischemic hypothermia with MK-801 treatment for 1 month group exhibited significant protective effects (not significant [P>0.05] compared with the control group). Extracellular glutamate levels for the intraischemic hypothermia group were significantly low, compared wi th the postischemic hypothermia group. There was no microglial activation i n the postischemic hypothermia at 1 week and 1 month after ischemia groups. Conclusion: Postischemic hypothermia and long-term intermittent administrat ion of MK-801 demonstrated significant neuronal protection, indicating that long-term glutamatergic activation, with changes in N-methyl-D-aspartate r eceptors, plays a role in neuronal damage in the chronic postischemic stage .