Effects of oxiracetam on the decrease in population spikes in hypoxic and low glucose media.

Evoked potentials were recorded in rat cerebral cortical slices. The amplitude of the evoked potential was reduced by perfusion with hypoxic (0-25%) or low glucose (0-5 mM) media in a concentration-dependent manner, and the evoked potentials disappeared under severe conditions (below 15% O2, below 3 mM glucose). We investigated the protective effects of oxiracetam on the decrease in evoked potentials under hypoxic (15% O2) and low glucose (3 mM glucose) conditions. Drugs were perfused from 45 min before hypoxic or low glucose perfusion to the end of the experiment. Oxiracetam (10(-6)-10(-5) M) dose-dependently minimized the amplitude reduction of evoked potentials and prolonged their disappearance time. At a concentration of 10(-5) M, oxiracetam protected against the disappearance of evoked potential in 5 of the 6 samples under hypoxic conditions and in all 6 samples under low glucose conditions. Indeloxazine (5 x 10(-6)-10(-5) M) and bifemelane (5 x 10(-6)-10(-5) M) prevented the reduction of the amplitude of evoked potentials under low glucose conditions. However, these drugs had no effect at a concentration of 10(-6) M. These data indicate that oxiracetam has a protective effect against neuronal dysfunction and that this effect develops at a lower concentration than those of indeloxazine and bifemelane.