NMDA antagonists prevent hypothermic injury and death of mammalian spinal neurons

J Neurotrauma. Winter 1990;7(4):229-36. doi: 10.1089/neu.1990.7.229.

Abstract

Prolonged (2-6 h) cooling of monolayer cultures of dissociated murine spinal cord at temperatures below 17 degrees C caused pronounced swelling of neuronal perikarya and dendrites. The numbers of swollen neurons in a culture increased as the temperature was reduced, and at 7 degrees C-10 degrees C all of the neurons were swollen. On rewarming the cultures to 37 degrees C, the majority of the swollen neurons died (up to 74% at 10 degrees C). Glial cells were not affected. Addition of the NMDA antagonists D-2-amino-5-phosphonovalerate (DAPV, 100 microM), ketamine (100 microM), and dibenzocyclohepteneimine (MK801, 10 microM) to spinal cord cultures before lowering the temperature to 10 degrees C minimized the dendrosomatic swelling and reduced neuronal mortality from 74% to 10%. These data show a surprising sensitivity of some neurons to nonfreezing low temperatures and suggest direct involvement of the NMDA receptor in hypothermia-related neuronal death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Cell Survival
  • Dizocilpine Maleate / pharmacology
  • Female
  • Freezing
  • Hypothermia, Induced / adverse effects*
  • Ketamine / pharmacology
  • Mice
  • N-Methylaspartate / antagonists & inhibitors*
  • Neurons / pathology*
  • Pregnancy
  • Spinal Cord Injuries / etiology
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / prevention & control*

Substances

  • N-Methylaspartate
  • Ketamine
  • Dizocilpine Maleate
  • 2-Amino-5-phosphonovalerate