In vitro investigations of the effects of nonfreezing low temperatures on lesioned and uninjured mammalian spinal neurons.
This two-part investigation explored the parameters and mechanisms of: (1) injury to spinal cord (SC) neurons by nonfreezing low temperatures, and (2) hypothermic protection of SC neurons subjected to a defined, physical injury (dendrite transection). Conclusions from the studies of hypothermic injury were: (1) morphologic and ultrastructural signs of stress developed in SC neurons as the temperature was decreased below 17 degrees C; (2) most neurons showing stress during cooling died upon rewarming to 37 degrees C; (3) spontaneous SC network activity was not significantly changed by cooling to 17 degrees C for 2 hours and rewarming, but cooling to 10 degrees C for 1 hour caused a reduction of burst frequency after rewarming, and cooling to 10 degrees C for 2 hours resulted in electrical silence after rewarming; and (4) application of N-methyl-D-aspartate (NMDA) antagonists before cooling prevented neuronal death, ultrastructural damage, and loss of activity upon rewarming, but application after cooling (before rewarming) was not protective. Conclusions from the studies of hypothermic protection were: (1) cooling at 17 degrees C for 2 hours followed by rewarming to 37 degrees C significantly increased lesioned neuron survival, but protection was lost when the period at 17 degrees C was increased to 6 hours; (2) NMDA blockade under normothermic (37 degrees C) or hypothermic (17 degrees C or 10 degrees C for 2 hours) conditions was not more protective of lesioned neurons than cooling to 17 degrees C (no NMDA antagonist); and (3) 200 microM thiopental or 100 microM pentobarbital increased lesioned neuron survival to a degree comparable to cooling for 2 hours at 17 degrees C.
Lucas
J H
JH
Department of Physiology, Ohio State University, Columbus.
Emery
D G
DG
Wang
G
G
Rosenberg-Schaffer
L J
LJ
Jordan
R S
RS
Gross
G W
GW
D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004594:Electrophysiology; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects* / Q000379:methods; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology*; D013874:Thiopental / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D010424:Pentobarbital; D013874:Thiopental