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 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.
Wilde
G J
GJ
Department of Clinical Neurological Sciences, University of Southampton, Southampton General Hospital, England, U.K.
Pringle
A K
AK
Wright
P
P
Iannotti
F
F
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D002545:Brain Ischemia; D016923:Cell Death; D005296:Ferrous Compounds / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D017665:Hydroxyl Radical / Q000494:pharmacology*; D002534:Hypoxia, Brain; D009474:Neurons / Q000187:drug effects; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000494:pharmacology*
D001557:Benzenesulfonates; D016227:Benzoquinones; D005296:Ferrous Compounds; D013481:Superoxides; C094272:N-tert-butyl-(2-sulfophenyl)nitrone; D017665:Hydroxyl Radical; C020748:ferrous sulfate; C034257:duroquinone