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 temperature s, 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 be low 17-degrees-C; (2) most neurons showing stress during cooling died upon rewarming to 37-degrees-C; (3) spontaneous SC network activity wa s 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) applicat ion of N-methyl-D-aspartate (NMDA) antagonists before cooling prevente d neuronal death, ultrastructural damage, and loss of activity upon re warming, but application after cooling (before rewarming) was not prot ective. Conclusions from the studies of hypothermic protection were: ( 1) cooling at 17-degrees-C for 2 hours followed by rewarming to 37-deg rees-C significantly increased lesioned neuron survival, but protectio n 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 protect ive of lesioned neurons than cooling to 17-degrees-C (no NMDA antagoni st); and (3) 200 muM thiopental or 100 muM pentobarbital increased les ioned neuron survival to a degree comparable to cooling for 2 hours at 17-degrees-C.