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Journal of neurochemistry

Differential vulnerability of the CA1 and CA3 subfields of the hippocampus to superoxide and hydroxyl radicals in vitro.


PMID 9231752

Abstract

The relative roles of the superoxide and hydroxyl radicals in oxidative stress-induced neuronal damage were investigated using organotypic hippocampal slice cultures. Cultures exposed to 100 microM duroquinone, a superoxide-generating compound, for 3 h developed CA1-selective lesions over a period of 24 h. The damage accounted for approximately 64% of the CA1 subfield, whereas CA3 showed just 6% damage, a pattern of damage comparable to that observed following hypoxia/ischaemia. Duroquinone-induced damage was attenuated by a spin-trap agent. In contrast, hydroxyl radical-mediated damage, generated by exposure to 30 microM ferrous sulphate for 1 h, resulted in a CA3-dominant lesion. The damage developed over 24 h, similar to that observed with duroquinone, but with approximately 45% damage in CA3 compared with only 7% in CA1. These data demonstrate a selective vulnerability of the CA1 pyramidal neurones to superoxide-induced damage and suggest that of the free radicals generated following hypoxia/ischaemia, superoxide, rather than hydroxyl radical, is instrumental in producing neuronal damage.

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