title: The role of hypothermia in the regulation of blood glutamate levels in naive rats.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Critical Care, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Matthew
authors.initials: M
authors.lastname: Boyko
authors.forename: Ruslan
authors.initials: R
authors.lastname: Kuts
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Gruenbaum
authors.forename: Israel
authors.initials: I
authors.lastname: Melamed
authors.forename: Shaun E
authors.initials: SE
authors.lastname: Gruenbaum
authors.forename: Moti
authors.initials: M
authors.lastname: Klein
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shapira
authors.forename: Alexander
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000097:blood*; D007036:Hypothermia, Induced; D007530:Isoflurane; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D018698:Glutamic Acid; D007530:Isoflurane; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase