Neuroprotection by 21-aminosteroids: Insights from latencies of anoxic terminal negativity in hippocampus slices of guinea pig

The protection of neuronal function by 21-aminosteroids against a hypoxic c hallenge was tested in guinea pig hippocampal slices. 21-aminosteroids, whi ch apart from a protective mechanism against membrane lipid peroxidation, p rovide direct membrane stabilizing effects, are reported. We tested whether the 21-aminosteroid U-74389G delays the anoxic terminal negativity (ATN) o f the DC-potential during hypoxia. Hippocampal slices were placed at the in terface of artificial cerebrospinal fluid (aCSF) and gaseous phase (normoxi c: 95% O-2, 5% CO2 hypoxic: 95% N-2, 5% CO2). Population spikes obtained by stimulation of Schaffer-collaterals as well as the DC-Potential were recor ded in the CA1 region. The latency of appearance of ATN alter oxygen depriv ation was determined In control experiments, the latency of ATN was 12.6 +/ - 3.1 min (n=6, mean +/- SEM). With application of U-74389G, the ATN-latenc y was 8.8 +/- 3.2 min (n = 6). We conclude that the cerebroprotective effec t of the 21-aminosteroid is not mediated via direct membrane stabilization.