The Effects of Mild and Deep Hypothermia on the Neuronal Activity and Energy Metabolism in Brain Slices In Vitro

Abstract

Using hippocampal slices of guinea pig, we have studied the effect of cooling and rewarming (8°–37°C) on the neuronal activity of pyramidal neurons of the CA3 region of hippocampus, and further examined the effect of hypothermia on the reversibility of the neural function and high-energy phosphates during long-lasting deprivation of oxygen and/or glucose. During gradual cooling of the perfusion medium containing oxygen and glucose from 37°C to 15°C, the amplitude of the field population potentials (PS) transiently increased at 31°C, and decayed with further cooling to extinction. During rewarming PS reappeared, while the amplitude increased to a maximum at 31°C and then decreased to the original level with further warming to 37°C. In the intracellular recording study of pyramidal neurons, hypothermia reduced the excitatory postsynaptic potential (EPSP) slope in a temperature-dependent manner, but the EPSP amplitude was enhanced transiently between 33°C and 28°C and decayed with further cooling. Neuronal activities including membrane properties recovered fully when the temperature was raised to 37°C even after long-term deep hypothermia (8°C). During deprivation of oxygen and/or glucose the survival period, the period of deprivation of oxygen and/or glucose during which neuronal activity of the tissue slice can show full recovery, was 10, 15, and 45 min at 37°C, 28°C, and 21°C, respectively. During deprivation of glucose only it was 1.5, 3, and 5h at 37°C, 28°C, and 21°C, and during deprivation of oxygen only it was 2.5,5, and 15 h at 37°C, 28°C, and 21°C, respectively. The concentration of adenosine triphosphate (ATP) and phosphocreatine (Per) showed good recovery in the slices with full neuronal reversibility. Deep hypothermia (21°C) markedly prolonged the survival period of neurons of tissue slices during deprivation of oxygen and/or glucose.