The role of hypothermia in the regulation of blood glutamate levels in naive rats

Matthew Boyko, Ruslan Kuts, Benjamin F. Gruenbaum, Israel Melamed, Shaun E. Gruenbaum, Moti Klein, Yoram Shapira, Alexander Zlotnik

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Pages (from-to)174-183
Number of pages10
JournalJournal of Neurosurgical Anesthesiology
Issue number2
StatePublished - 1 Apr 2013
Externally publishedYes


  • glutamate
  • glutamate oxaloacetate transaminase (GOT)
  • glutamate pyruvate transaminase (GPT)
  • hypothermia
  • neuroprotection

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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