Different effects between thiopental and isoflurane on recovery from brief hypoxia in rat hippocampal slices in vitro

Although many reports suggested that general anesthetic agents, especially barbiturate, could prevent the damage induced by hypoxia in the central nervous system in vivo and in vitro, the cellular mechanisms by which general anesthetics attenuate the hypoxic neuronal damage remain uncertain. We have studied the effects of hypoxic hypoxia on the evoked field potential of hippocampal CA1 in the absence and presence of thiopental and isoflurane. Extracellular recordings were used to record population spikes (PSs) in CA1 pyramidal neurons of rat hippocampal slices, stimulated electrically via Schaffer collateral fibers input. The paired-stimuli (interstimulus interval=40 ms) were employed to induce the paired-pulse facilitation (PPF=PS2/PS1). Hypoxic hypoxia (10%O₂) was applied to slices by switching the gas mixture from 95%O₂/5%CO₂ to 10%CO₂/85%N₂/5%CO₂ for 3 min in the absence and presence of general anesthetics. In the absence of general anesthetics, PPF increased during hypoxic hypoxia due to the enhancement of PS2. The PS1 gradually recovered to the pre-hypoxic level following re-oxygenation. Thiopental (2 × 10^-4 M) attenuated the enhancement of PS2 during hypoxia, and accelerated the recovery of PS1 from hypoxia. In contrast, isoflurane (0.7 vol%) strongly increased PPF, due to the enhancement of PS2 and the depression of PS1 during hypoxia. Isoflurane failed to improve the recovery response from hypoxia. Pre-treatment of thiopental, but not isoflurane, accelerated the recovery from brief hypoxia. The prophylactic effects might arise from the depression of PPF during hypoxia in the presence of thiopental.