T. Nakamura et al., Long-term activation of the glutamatergic system associated with N-methyl-D-aspartate receptors after postischemic hypothermia in gerbils, NEUROSURGER, 49(3), 2001, pp. 706-713
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
.