The protective effect of hypothermia on hippocampal slices from guinea pig during deprivation of oxygen and glucose

Using guinea pig hippocampal slice preparations, the effect of temperature on the electrical activity and the protective effect of hypothermia against deprivation of both oxygen and glucose were studied by recording field potentials of pyramidal cell layer (CA 3–4 area) and by measuring the content of adenosine triphosphate (ATP), phosphocreatine (PCr) and lactate of each slice. Cooling the perfusion medium from 37 to 21 °C caused a decrease in the amplitude of field potentials, although the amplitude increased (120%) transiently at around 33 °C. The electrical activity ceased at around 22 °C. When the temperature was raised from 21 to 37 °C, the activity recovered reversibly. However, when the temperature was raised to above 38 °C, the amplitude decreased and disappeared irreversibly at 42 °C. During deprivation, energy consumption (total ∼P used;2 × ΔATP+ ΔPCr+ 1.3 × Δlactate) was suppressed by lowering the tissue temperature and the initial (0–2.5 min deprivation) energy use rate was calculated to be 42.2 at 37°C, 22.8 at 28 °C and 7.0 at 21 °C (∼P m mol/kg protein/min), respectively. From these values, Q10 was estimated to be 2.05. With regard to the protective effect of hypothermia, the critical survival time (period of deprivation of oxygen and glucose for the complete recovery in neural activity and the level of high energy phosphates) was 10 min at 37 °C, 15 min at 28 °C, and 45 min at 21 °C, respectively. These results indicate that moderate hypothermia (28 °C) is not very effective in protecting the brain tissue against deprivation of oxygen and glucose, and that deep hypothermia (21 °C) has a much more potent protective effect against deprivation from the functional and metabolic viewpoint.