The effects of thiopental on spreading depression induced by anoxia in the rat hippocampal slice in vitro

"Spreading depression" (SD) is a phenomenon that occurs soon after beginning of severe hypoxia or ischemia of central nervous system. It consists of a synchronous, sudden and profound depolarization of a population of neurons. Since strong evidence implicates SD as an important factor in neural damage caused by hypoxia/ischemia, treatments that prevent the occurrence of SD may provide neuronal protection. Although, it has been reported that general anesthetics (especially, barbiturate) can mitigate ischemic damages, the mechanisms of this protection against hypoxia/ischemia remain unclear. Recently, we reported that thiopental could prevent the occurrence of SD during 3 min anoxia on rat hippocampal slice in vitro. Therefore, we decided to determine the mechanisms by which thiopental could prevent occurring SD, using antidromically elicited population spike (PS) in response to the activation of non-synaptic pathways. Extracellular recordings were used to record population spikes (PSs) in CA1 pyramidal neurons of rat hippocampal slices, stimulated electrically via alveus hippocampi. Anoxia (0% O₂) was applied to slices by switching the gas mixture from 95%O₂/5%CO₂ to 95%N₂/5%CO₂ for 3 min in the absence and presence of 2 × 10^-4 M thiopental. To make complete block of neurotransmission, NMDA receptor antagonist, non-NMDA receptor antagonist, and GABA receptor antagonist were applied to the perfusate. One-to 3 min after oxygen withdrawal there was a sudden large negative shift of field potential. Extracellular potential returned rapidly toward its control level following re-oxygenation in all slices. In the absence of thiopental, SD occurred in 89% of slices. By contrast, thiopental could significantly prevent from occurring the SD (5.9%). Together with previous results, thiopental could significantly prevent the occurrence of SD independent of synaptic transmission. Current study suggested that thiopental might protect brain tissue against hypoxia by preventing the occurrence of SD, and that its mechanism could not relate to modulation of excitatory and inhibitory neurotransmission.