Effects of Pre- and Postischemic Administration of Thiopental on Transmitter Amino Acid Release and Histologic Outcome in Gerbils

Abstract

Background The mechanism by which barbiturates protect neurons against ischemia is unclear, particularly when they are given after ischemia or reperfusion begins. Because an excess release of excitatory neurotransmitters causes postsynaptic membrane depolarization, which triggers neuronal damage in ischemia, the effects of thiopental on histologic outcome, ischemia-induced amino acid release, and anoxic depolarization in gerbils were studied. Methods The effects of different doses of thiopental administered before or after ischemia were examined morphologically by assessing delayed neuronal death in hippocampal CA1 pyramidal cells produced by forebrain ischemia for 3 min in gerbils. The ischemia-induced changes in output of aspartate, glutamate, glycine, taurine, and gamma-aminobutyric acid were measured using a microdialysis-high-performance liquid chromatography procedure, and the differences among a halothane-anesthetized group, a thiopental-administered group, and a group given thiopental after a period of ischemia were evaluated. The changes induced in the direct-current potential in the hippocampal CA1 area by forebrain ischemia were compared in animals anesthetized with halothane and those given thiopental. Results Preischemic administration of thiopental at all doses decreased the risks for delayed neuronal death (P < 0.01). Post-ischemic administration at a dosage of 2 mg.kg-1.min-1 for 60 min protected neurons, but the same dose for 10 min did not ameliorate the cell injury. Forebrain ischemia produced marked increases in all amino acids 3 to 6 min after the start of recirculation in the halothane-anesthetized gerbils, whereas thiopental anesthesia (2 mg.kg-1.min-1) reduced these increases throughout the experimental period, except for glycine (P < 0.01). The initiation of thiopental after reflow did not markedly diminish these increases. Thiopental anesthesia prolonged the onset of anoxic depolarization and reduced its maximal amplitude. Conclusions Thiopental helps protect the brain from ischemia, although treatment with this agent after ischemia requires a larger dose than that before ischemia. The effect of preischemic treatment may be related to the suppression of the excitatory amino acid release and the direct-current potential shift.