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 challenge was tested in guinea pig hippocampal slices. 21-aminosteroids, which apart from a protective mechanism against membrane lipid peroxidation, provide direct membrane stabilizing effects, are reported. We tested whether the 21-aminosteroid U-74389G delays the anoxic terminal negativity (ATN) of the DC-potential during hypoxia. Hippocampal slices were placed at the interface of artificial cerebrospinal fluid (aCSF) and gaseous phase (normoxic: 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 recorded in the CA1 region. The latency of appearance of ATN alter oxygen deprivation 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-latency was 8.8 +/- 3.2 min (n = 6). We conclude that the cerebroprotective effect of the 21-aminosteroid is not mediated via direct membrane stabilization.