title: Neuroprotection by 21-aminosteroids: insights from latencies of anoxic terminal negativity in hippocampus slices of guinea pig.
abstract: 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% O2, 5% CO2; hypoxic: 95% N2, 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 after 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.
mesh_terms: D000818:Animals; D003080:Cold Temperature; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D002534:Hypoxia, Brain / Q000188:drug therapy*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011281:Pregnatrienes / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects