Overexpression of SOD1 in Transgenic Rats Protects Vulnerable Neurons Against Ischemic Damage After Global Cerebral Ischemia and Reperfusion
| Autor: | Charles J. Epstein, Bernard Calagui, Sylvia F. Chen, Makoto Kawase, Elaine J. Carlson, Kensuke Murakami, Liza Reola, Pak H. Chan, Yibing Li |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Cell Survival SOD1 Ischemia Striatum DNA Fragmentation Biology Hippocampal formation Neuroprotection Hippocampus Article Animals Genetically Modified Rats Sprague-Dawley Cresyl violet chemistry.chemical_compound Superoxide Dismutase-1 Pregnancy Superoxides Internal medicine medicine In Situ Nick-End Labeling Animals Neurons Cell Death Superoxide Superoxide Dismutase General Neuroscience Dentate gyrus medicine.disease Rats Endocrinology chemistry nervous system Ischemic Attack Transient Cerebrovascular Circulation Reperfusion Injury Nerve Degeneration Female Neuroscience |
| Popis: | Transient global cerebral ischemia resulting from cardiac arrest is known to cause selective death in vulnerable neurons, including hippocampal CA1pyramidal neurons. It is postulated that oxygen radicals, superoxide in particular, are involved in cell death processes. To test this hypothesis, we first usedin situimaging of superoxide radical distribution by hydroethidine oxidation in vulnerable neurons. We then generated SOD1 transgenic (Tg) rats with a five-fold increase in copper zinc superoxide dismutase activity. The Tg rats and their non-Tg wild-type littermates were subjected to 10 min of global ischemia followed by 1 and 3 d of reperfusion. Neuronal damage, as assessed by cresyl violet staining and DNA fragmentation analysis, was significantly reduced in the hippocampal CA1region, cortex, striatum, and thalamus in SOD1 Tg rats at 3 d, as compared with the non-Tg littermates. There were no changes in the hippocampal CA3subregion and dentate gyrus, resistant areas in both SOD1 Tg and non-Tg rats. Quantitative analysis of the damaged CA1subregion showed marked neuroprotection against transient global cerebral ischemia in SOD1 Tg rats. These results suggest that superoxide radicals play a role in the delayed ischemic death of hippocampal CA1neurons. Our data also indicate that SOD1 Tg rats are useful tools for studying the role of oxygen radicals in the pathogenesis of neuronal death after transient global cerebral ischemia. |
| Databáze: | OpenAIRE |
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