gms | German Medical Science

Methohexital is commonly used as a neuroprotectant in clinical situations of diminished brain perfusion. Former experiments have shown a favourable electrophysiologic effect in vitro. Barbiturates are known to possess a GABAergic effect for themselves. On the other hand, changes of neurotransmitter release are another possible mechanism by which barbiturates could exert their neuroprotective effects. We asked whether ischemic brain tissue shows changes in the interstitial release of amino acids, especially neurotransmitters, under the influence of methohexital.

Rat hippocampal brain slices were kept in an interface (gaseous/aqueous phase) in vitro environment. DC and evoked potentials were registered together with sampling of intercellular fluid by in vitro microdialysis. Ischemia was simulated by simultaneous withdrawal of oxygen and glucose. Methohexital concentrations of 40 (n=8), 90 (n=6), and 140 μmol/l (n=7) were applied, and each experiment was pair-matched with a control. Latency and amplitude of anoxic depolarization as well as postischemic recovery of evoked potentials were studied, while 5 min-microdialysis samples were examined for a range of amino acids including major neurotransmitters by HPLC.

Typical changes of electrophysiologic as well as biochemical measurements are demonstrated in the slices as soon as ischemia is induced. Methohexital, however, did not change either kinetics or spectrum of amino acid release in any of the applied concentrations, nor did it alter the electrophysiologic response to ischemic stress.

Our model was not able to show significant barbiturate-dependent changes of the release characteristics of so-called excitotoxic amino acids in particular. Therefore the inherent GABAergic activity of barbiturates remains one of the more likely ways by which these drugs act neuroprotectively.