Thiopental attenuates hypoxic changes of electrophysiology, biochemistry, and morphology in rat hippocampal slice CA1 pyramidal cells

Background and Purpose-Thiopental has been shown to protect against cerebra l ischemic damage; however, it has undesirable side effects. We have examin ed how thiopental alters histological, physiological, and biochemical chang es during and after hypoxia, These experiments should enable the discovery of agents that share some of the beneficial effects of thiopental. Methods-We made intracellular recordings and measured ATP, sodium, potassiu m, and calcium concentrations from CA1 pyramidal cells in rat hippocampal s lices subjected to 10 minutes of hypoxia with and without 600 mu mol/l. thi opental. Results-Thiopental delayed the time until complete depolarization (21+/-3 v ersus 11+/-2 minutes for treated versus untreated slices, respectively) and attenuated the level of depolarization at 10 minutes of hypoxia (-33+/-6 v ersus -12+/-5 mV). There was improved recovery of the resting potential aft er 10 minutes of hypoxia in slices treated with thiopental (89% versus 31% recovery). Thiopental attenuated the changes in sodium (140% versus 193% of prehypoxic concentration), potassium (62% versus 46%), and calcium (111% v ersus 197%) during 18 minutes of hypoxia, There was only a small effect on ATP (18% versus 8%). The percentage of cells showing clear histological dam age was decreased by thiopental (45% versus 71%), and thiopental improved p rotein synthesis after hypoxia (75% versus 20%). Conclusions-Thiopental attenuates neuronal depolarization, an increase in c ellular sodium and calcium concentrations, and a decrease in cellular potas sium and ATP concentrations during hypoxia, These effects may explain the r educed histological, protein synthetic, and electrophysiological damage to CA1 pyramidal cells after hypoxia with thiopental.