NMDA antagonists prevent hypothermic injury and death of mammalian spinal neurons.
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.
Lucas
J H
JH
Center for Network Neuroscience, University of North Texas, Denton.
Wang
G F
GF
Gross
G W
GW
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D005615:Freezing; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007649:Ketamine / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000473:pathology*; D011247:Pregnancy; D013119:Spinal Cord Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate