DIFFERENTIAL VULNERABILITY OF THE CA1 AND CA3 SUBFIELDS OF THE HIPPOCAMPUS TO SUPEROXIDE AND HYDROXYL RADICALS IN-VITRO

The relative roles of the superoxide and hydroxyl radicals in oxidativ e stress-induced neuronal damage were investigated using organotypic h ippocampal slice cultures. Cultures exposed to 100 mu M duroquinone, a superoxide-generating compound, for 3 h developed CA1-selective lesio ns over a period of 24 h. The damage accounted for similar to 64% of t he CA1 subfield, whereas CA3 showed just 6% damage, a pattern of damag e comparable to that observed following hypoxia/ischaemia. Duroquinone -induced damage was attenuated by a spin-trap agent. In contrast, hydr oxyl radical-mediated damage, generated by exposure to 30 mu M ferrous sulphate for 1 h, resulted in a CA3-dominant lesion. The damage devel oped over 24 h, similar to that observed with duroquinone, but with si milar to 45% damage in CA3 compared with only 7% in CA1. These data de monstrate a selective vulnerability of the CA1 pyramidal neurones to s uperoxide-induced damage and suggest that of the free radicals generat ed following hypoxia/ischaemia, superoxide, rather than hydroxyl radic al, is instrumental in producing neuronal damage.