Brain temperature modifies glutamate neurotoxicity in vivo

J Neurotrauma. 1999 Apr;16(4):285-97. doi: 10.1089/neu.1999.16.285.


The purpose of this study was to examine the effects of mild hypothermia and hyperthermia on glutamate excitotoxicity. Glutamate-induced cortical lesions were produced in hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (40 degrees C) rats by perfusion of a 0.5 M glutamate solution via a microdialysis probe. The volume of the lesion 7 days after glutamate perfusion was quantified histologically by image analysis. This histological assessment was performed in two experiments; in one, each of the target temperatures was induced before glutamate perfusion, and in the other, each of the target temperatures was induced after stopping the glutamate perfusion. We also examined the effect of temperature on the diffusion of exogenously delivered material in the extracellular space using autoradiography of the perfused glutamate solution containing 14C-labeled sucrose. In the two experiments in which each of the target temperatures was induced before or after glutamate perfusion, the volume of damage was reduced by mild hypothermia and enlarged by mild hyperthermia. The volume of 14C diffusion also increased as brain temperature increased. These results provide evidence that small variations of brain temperature modify glutamate excitotoxicity. The results also suggest that the change in glutamate diffusion in the extracellular space is one mechanism by which mild hypothermia and hyperthermia exert their protective and harmful effects respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Body Temperature*
  • Brain / drug effects*
  • Brain / pathology
  • Brain Injuries / chemically induced*
  • Brain Injuries / pathology
  • Carbon Radioisotopes
  • Disease Models, Animal
  • Disease Progression
  • Glutamic Acid / administration & dosage
  • Glutamic Acid / pharmacokinetics
  • Glutamic Acid / toxicity*
  • Hyperthermia, Induced / adverse effects
  • Hypothermia, Induced
  • Male
  • Microdialysis
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Neurons / drug effects
  • Neurons / pathology
  • Rats
  • Rats, Wistar
  • Sucrose / pharmacokinetics
  • Time Factors


  • Carbon Radioisotopes
  • Glutamic Acid
  • Sucrose