EFFECTS OF PREISCHEMIC AND POSTISCHEMIC ADMINISTRATION OF THIOPENTAL ON TRANSMITTER AMINO-ACID RELEASE AND HISTOLOGIC OUTCOME IN GERBILS

Background: The mechanism by which barbiturates protect neurons agains t ischemia is unclear, particularly when they are given after ischemia or reperfusion begins. Because an excess release of excitatory neurot ransmitters causes postsynaptic membrane depolarization, which trigger s neuronal damage in ischemia, the effects of thiopental on histologic outcome, ischemia-induced amino acid release, and anoxic depolarizati on in gerbils mere studied. Methods: The effects of different doses of thiopental administered before or after ischemia were examined morpho logically by assessing delayed neuronal death in hippocampal CA1 pyram idal cells produced by forebrain ischemia for 3 min in gerbils. The is chemia-induced changes in output of aspartate, glutamate, glycine, tau rine, 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 evaluate d. The changes induced in the direct-current potential in the hippocam pal CA1 area by forebrain ischemia were compared in animals anesthetiz ed with halothane and those given thiopental. Results: Preischemic adm inistration of thiopental at all doses decreased the risks for delayed neuronal death (P < 0.01). Postischemic administration at a dosage of 2 mg . kg(-1) . min(-1) for 60 min protected neurons, but the same do se for 10 min did not ameliorate the cell injury. Forebrain ischemia p roduced marked increases in all amino acids 3 to 6 min after the start of recirculation in the halothane-anesthetized gerbils, whereas thiop ental anesthesia (2 mg . kg(-1) . min(-1)) reduced these increases thr oughout the experimental period, except for glycine (P < 0.01). The in itiation of thiopental after reflow did not markedly diminish these in creases. Thiopental anesthesia prolonged the onset of anoxic depolariz ation and reduced its maximal amplitude. Conclusions: Thiopental helps protect the brain from ischemia, although treatment with this agent a fter ischemia requires a larger dose than that before ischemia. The ef fect of preischemic treatment may be related to the suppression of the excitatory amino acid release and the direct-current potential shift.