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dc.contributor.authorRaz, Limor
dc.contributor.authorZhang, Quan-Guang
dc.contributor.authorZhou, Cai-feng
dc.contributor.authorHan, Dong
dc.contributor.authorGulati, Priya
dc.contributor.authorYang, Li-cai
dc.contributor.authorYang, Fang
dc.contributor.authorWang, Rui-min
dc.contributor.authorBrann, Darrell W
dc.date.accessioned2012-10-26T16:26:49Z
dc.date.available2012-10-26T16:26:49Z
dc.date.issued2010-09-7en_US
dc.identifier.citationPLoS One. 2010 Sep 7; 5(9):e12606en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid20830300en_US
dc.identifier.doi10.1371/journal.pone.0012606en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/593
dc.description.abstractBackground: Recent work by our laboratory and others has implicated NADPH oxidase as having an important role in reactive oxygen species (ROS) generation and neuronal damage following cerebral ischemia, although the mechanisms controlling NADPH oxidase in the brain remain poorly understood. The purpose of the current study was to examine the regulatory and functional role of the Rho GTPase, Rac1 in NADPH oxidase activation, ROS generation and neuronal cell death/cognitive dysfunction following global cerebral ischemia in the male rat.
dc.description.abstractMethodology/Principal Findings: Our studies revealed that NADPH oxidase activity and superoxide (O2â ) 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 O2â production at 3 h after stroke as compared to vehicle-treated controls. NSC23766 also attenuated â in situâ O2â 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 7â 9 d post reperfusion as compared to vehicle-treated animals.
dc.description.abstractConclusions/Significance: The results of the study suggest that Rac1 GTPase has a critical role in mediating ischemia/reperfusion injury-induced NADPH oxidase activation, ROS generation and oxidative stress in the hippocampal CA1 region of the rat, and thus contributes significantly to neuronal degeneration and cognitive dysfunction following cerebral ischemia.
dc.rightsRaz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectNeuroscienceen_US
dc.subjectNeuroscience/Neurobiology of Disease and Regenerationen_US
dc.subjectNeuroscience/Neuronal Signaling Mechanismsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBrain Ischemiaen_US
dc.subject.meshCognitionen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshHippocampusen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshNADPH Oxidaseen_US
dc.subject.meshOxidative Stressen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReactive Oxygen Speciesen_US
dc.subject.meshrac1 GTP-Binding Proteinen_US
dc.titleRole of Rac1 GTPase in NADPH Oxidase Activation and Cognitive Impairment Following Cerebral Ischemia in the Raten_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2935374en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics
refterms.dateFOA2019-04-09T22:21:35Z
html.description.abstractBackground: Recent work by our laboratory and others has implicated NADPH oxidase as having an important role in reactive oxygen species (ROS) generation and neuronal damage following cerebral ischemia, although the mechanisms controlling NADPH oxidase in the brain remain poorly understood. The purpose of the current study was to examine the regulatory and functional role of the Rho GTPase, Rac1 in NADPH oxidase activation, ROS generation and neuronal cell death/cognitive dysfunction following global cerebral ischemia in the male rat.
html.description.abstractMethodology/Principal Findings: Our studies revealed that NADPH oxidase activity and superoxide (O2â ) 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 O2â production at 3 h after stroke as compared to vehicle-treated controls. NSC23766 also attenuated â in situâ O2â 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 7â 9 d post reperfusion as compared to vehicle-treated animals.
html.description.abstractConclusions/Significance: The results of the study suggest that Rac1 GTPase has a critical role in mediating ischemia/reperfusion injury-induced NADPH oxidase activation, ROS generation and oxidative stress in the hippocampal CA1 region of the rat, and thus contributes significantly to neuronal degeneration and cognitive dysfunction following cerebral ischemia.


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