Oxidative stress and neuronal death/survival signaling in cerebral ischemia |
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Authors: | Atsushi Saito Carolina M Maier Purnima Narasimhan Tatsuro Nishi Yun Seon Song Fengshan Yu Jing Liu Yong-Sun Lee Chikako Nito Hiroshi Kamada Robert L Dodd Lily B Hsieh Benjamin Hassid Esther E Kim Maricela González Pak H Chan |
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Institution: | Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. |
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Abstract: | It has been demonstrated by numerous studies that apoptotic cell death pathways are implicated in ischemic cerebral injury in ischemia models in vivo. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and the numerous reports suggest the involvement of cell survival/death signaling pathways in the pathogenesis of apoptotic cell death in ischemic lesions. In these models, reoxygenation during reperfusion provides oxygen as a substrate for numerous enzymatic oxidation reactions and for mitochondrial oxidative phosphorylation to produce adenosine triphosphate. Oxygen radicals, the products of these biochemical and physiological reactions, are known to damage cellular lipids, proteins, and nucleic acids and to initiate cell signaling pathways after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in the signaling pathways has provided substantial understanding of the mechanisms involved in cell death/survival signaling pathways and the role of oxygen radicals in ischemic cerebral injury. Future studies of these pathways could provide novel therapeutic strategies in clinical stroke. |
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