Abstract SNACC-40

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Effect of nasopharyngeal cooling on the dynamic changes in extracellular glutamate levels during anoxic depolarization and repolarization

Sato S, Takeda Y, Kawase H, Mizoue R, Morimatsu H
Okayama University Graduate School of Medicine, Okayama, , Japan

Intraischemic hypothermia is effective in neuroprotection. We found that brain hypothermia induced after depolarization lowered the cerebral blood flow (CBF) threshold for repolarization. We hypothesized that recovery of depolarization was related to the extracellular glutamate levels. In this study, we examined the dynamic changes in the extracellular glutamate levels during anoxic depolarization and repolarization.
Methods: Two groups of 10 rats each formed the normothermic and hypothermic groups. A microdialysis probe for measuring the glutamate levels was inserted in the right parietal cortex adjacent to the direct current (DC) electrode and Laser– Doppler flow probe. Following bilateral common carotid artery occlusion, the CBF was continuously decreased by exsanguination at the speed of 5% of the baseline level every 2 min until depolarization occurred. After 5 min of ischemic depolarization, the CBF was restored at the same rate until a positive DC shift was observed. In the normothermic group, the rats’s cerebral and rectal temperatures were maintained at 37 ± 0.5°C. In the hypothermic group, nasopharyngeal cooling was initiated immediately after the onset of anoxic depolarization. The cerebral temperature was reduced to 31 ± 0.5°C after approximately 5 minutes. Histological examination was performed using hematoxylin-eosin staining 5 days after the ischemic insult.
Results: In the hypothermic group, the brain temperature reduced to 31 ± 0.5°C at 4.7 ± 0.5 min after the onset of nasopharyngeal cooling. In the normothermic group, from the onset of depolarization until 5mins later, the glutamate levels continued to increase. In the hypothermic group, the glutamate levels started to decrease at 5 min after depolarization. The maximum extracellular glutamate levels were significantly lower (p < 0.01) for the hypothermic group (157.6 ± 101.8 μmol/L) than for the normothermic group (376.2 ± 123.7 μmol/L). In both the groups, repolarization occurred after extracellular glutamate levels started to decrease. At the start of repolarization, the extracellular glutamate levels in the two groups were 128.1 ± 98.3 μmol/L vs. 306.9 ± 151.3 μmol/L (p < 0.01), respectively. The CBF threshold for repolarization in the hypothermic group (26.3 ± 9.3 %) was significantly lower (p= 0.03) than in the normothermic group (44.3 ± 22.9 %). The percentages of neuronal damage in the two groups were 39.1 ± 15.1 % and 65.6 ± 15.7 % (p < 0.01), respectively, in the cerebral cortex, and 32.6 ± 18.7 % and 88.6 ± 14.0 % (p < 0.01), respectively, in the CA1 layer.
Conclusion: We presumed it was necessary that glutamate should be washed off or should undergo uptake into cells in order to generate repolarization. Decrease in the extracellular glutamate levels by intraischemic nasopharyngeal cooling seems to be involved in mechanisms that decrease the CBF threshold for repolarization and attenuate neuronal damage.
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