- Background: The exact mechanism of hypothermia-induced neuroprotection has not been determined yet; however, we hypothesized that it may be mediated by a blood glutamate-scavenging effect. Here, we examine the effect of hypothermic conditions (mild, moderate, and deep) on blood glutamate levels in naive rats. To identify the mechanism of hypothermia-induced glutamate reduction, we also measured concentrations of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), the primary regulators of glutamate concentration in blood. Methods: Rats were anesthetized with isoflurane, and their rectal temperature was maintained for 6 hours at 36 to 37°C, 33 to 36°C, 30 to 32°C, 18 to 22°C, or was not maintained artificially. At 6 hours, active cooling was discontinued and rats were allowed to rewarm. There were 12 rats in each group for a total of 60 rats. Blood samples were drawn at 0, 3, 6, 12, 24, and 48 hours for the determination of blood glutamate, GOT, and GPT levels. Results: A strong correlation between body temperature and blood glutamate levels was observed (P<0.001). Mild (33 to 36°C) and moderate (30 to 32°C) hypothermia led to reduced blood glutamate levels (P<0.001). Deep hypothermia (18 to 22°C) was associated with significant elevations in blood glutamate levels (P<0.001). Hypothermia, irrespective of the degree, led to elevations in GOT in plasma (P<0.001). Conclusions: Mild and moderate hypothermia led to a reduction in blood glutamate levels in rats, whereas deep hypothermia was associated with a significant elevation in blood glutamate levels. We further demonstrated an elevation of GOT and GPT levels, supporting their involvement in reducing blood glutamate by the conversion of glutamate to 2-ketoglutarate. We suggest that the neuroprotective properties of hypothermia may be partially because of a blood glutamate-scavenging mechanism.