NMDA Antagonists Prevent Hypothermic Injury and Death of Mammalian Spinal Neurons

Abstract

Prolonged (2–6 h) cooling of monolayer cultures of dissociated murine spinal cord at temperatures below 17°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°C–10°C all of the neurons were swollen. On rewarming the cultures to 37°C, the majority of the swollen neurons died (up to 74% at 10°C). Glial cells were not affected. Addition of the NMDA antagonists d-2-amino-5-phosphonovalerate (DAPV, 100 μM), ketamine (100 μM), and dibenzocyclohepteneimine (MK801, 10 μM) to spinal cord cultures before lowering the temperature to 10°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.