Determination of the target temperature required to block increases in extracellular glutamate levels during intraischemic hypothermia

This study aimed to determine a target temperature for intraischemic hypothermia that can block increases in extracellular glutamate levels. Two groups of 10 rats each formed the normothermia and intraischemic hypothermia groups. Extracellular glutamate levels, the extracellular potential, and the cerebral blood flow were measured at the adjacent site in the right parietal cerebral cortex. Cerebral ischemia was induced by occlusion of the bilateral common carotid arteries and hypotension. In the intraischemic hypothermia group, brain hypothermia was initiated immediately after the onset of membrane potential loss. In the normothermia group, extracellular glutamate levels began to increase simultaneously with the onset of membrane potential loss and reached a maximum level of 341.8 ± 153.1 μmol·L^-1. A decrease in extracellular glutamate levels was observed simultaneously with the onset of membrane potential recovery. In the intraischemic hypothermia group, extracellular glutamate levels initially began to increase, similarly to those in the normothermia group, but subsequently plateaued at 140.5 ± 105.4 μmol·L^-1, when the brain temperature had decreased to <32.6°C ± 0.9°C. A decrease in extracellular glutamate levels was observed simultaneously with the onset of membrane potential recovery, similarly to the findings in the normothermia group. The rate of decrease in extracellular glutamate levels was the same in both groups (-36.6 and-36.0 μmol·L^-1 in the normothermia and intraischemic hypothermia groups, respectively). In conclusion, the target temperature for blocking glutamate release during intraischemic hypothermia was found to be 32.6°C ± 0.9°C. Our results suggest that the induction of intraischemic hypothermia can maintain low glutamate levels without disrupting glutamate reuptake. Institutional protocol number: OKU-2016146.