Mild hypothermia--a revived countermeasure against ischemic neuronal damages

Neurosci Res. 1998 Oct;32(2):103-17. doi: 10.1016/s0168-0102(98)00076-5.


Although hypothermia as a means of cerebral protection against and resuscitation from ischemic damage has a history of approximately six decades, extensive studies, both in basic and clinical fields, on the mechanisms, effects and methods of mild hypothermia at temperatures no less than 31 degrees C have started only in the last decade. In experiments on rodents, hypothermia in the postischemic period that is introduced up to several hours after reperfusion and is maintained for one day followed by a slow rewarming, significantly protects hippocampal neurons against damage. The mode of action of hypothermia is apparently non-specific and multi-focal in widely progressing cascade reactions in ischemic cells; namely, suppressing: (1) glutamate surge followed by; (2) intraneuronal calcium mobilization; (3) sustained activation of glutamate receptors; (4) dysfunction of blood brain barrier; (5) proliferation of microglial cells; and (6) production of superoxide anions and nitric oxide. In addition, mild hypothermia modulates processes in ischemic condition at the level of cell nucleus, such as the binding of transcription factor AP-1 to DNA, and ameliorates the depression of protein synthesis. This non-specific and widely affecting manner might explain why hypothermia is superior to any medicine developed. Recent clinical trials of mild hypothermia in various individual institutions have revealed significantly beneficial outcomes in some cases, along with an accumulation of practical knowledge of techniques and treatments. Large scale randomized studies involving multiple institutions as well as exchange of informations and ideas are needed for further development of hypothermia treatment.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Animals
  • Brain Edema / physiopathology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / prevention & control
  • Brain Ischemia / therapy*
  • Cryotherapy / history
  • Disease Models, Animal
  • Excitatory Amino Acids / adverse effects
  • Fever / physiopathology
  • Gene Expression / physiology
  • History, 20th Century
  • Humans
  • Hypothermia, Induced* / history
  • Hypothermia, Induced* / methods
  • Microglia / metabolism


  • Excitatory Amino Acids