Abstract | BACKGROUND: METHODOLOGY/PRINCIPAL FINDINGS: Our studies revealed that NADPH oxidase activity and superoxide (O(2)(-)) production in the hippocampal CA1 region increased rapidly after cerebral ischemia to reach a peak at 3 h post-reperfusion, followed by a fall in levels by 24 h post-reperfusion. Administration of a Rac GTPase inhibitor ( NSC23766) 15 min before cerebral ischemia significantly attenuated NADPH oxidase activation and O(2)(-) production at 3 h after stroke as compared to vehicle-treated controls. NSC23766 also attenuated "in situ" O(2)(-) production in the hippocampus after ischemia/reperfusion, as determined by fluorescent oxidized hydroethidine staining. Oxidative stress damage in the hippocampal CA1 after ischemia/reperfusion was also significantly attenuated by NSC23766 treatment, as evidenced by a marked attenuation of immunostaining for the oxidative stress damage markers, 4-HNE, 8-OHdG and H2AX at 24 h in the hippocampal CA1 region following cerebral ischemia. In addition, Morris Water maze testing revealed that Rac GTPase inhibition after ischemic injury significantly improved hippocampal-dependent memory and cognitive spatial abilities at 7-9 d post reperfusion as compared to vehicle-treated animals. CONCLUSIONS/SIGNIFICANCE:
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Authors | Limor Raz, Quan-Guang Zhang, Cai-feng Zhou, Dong Han, Priya Gulati, Li-cai Yang, Fang Yang, Rui-min Wang, Darrell W Brann |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 9
Pg. e12606
(Sep 07 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 20830300
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Reactive Oxygen Species
- NADPH Oxidases
- Rac1 protein, rat
- rac1 GTP-Binding Protein
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Topics |
- Animals
- Brain Ischemia
(enzymology, metabolism, psychology)
- Cognition
- Disease Models, Animal
- Enzyme Activation
- Hippocampus
(enzymology, metabolism)
- Humans
- Male
- NADPH Oxidases
(genetics, metabolism)
- Oxidative Stress
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
(metabolism)
- rac1 GTP-Binding Protein
(genetics, metabolism)
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