title: Role of neuronal NADPH oxidase 1 in the peri-infarct regions after stroke.
abstract: The molecular mechanism underlying the selective vulnerability of neurons to oxidative damage caused by ischemia-reperfusion (I/R) injury remains unknown. We sought to determine the role of NADPH oxidase 1 (Nox1) in cerebral I/R-induced brain injury and survival of newborn cells in the ischemic injured region. Male Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO) followed by reperfusion. After reperfusion, infarction size, level of superoxide and 8-hydroxy-2'-deoxyguanosine (8-oxo-2dG), and Nox1 immunoreactivity were determined. RNAi-mediated knockdown of Nox1 was used to investigate the role of Nox1 in I/R-induced oxidative damage, neuronal death, motor function recovery, and ischemic neurogenesis. After I/R, Nox1 expression and 8-oxo-2dG immunoreactivity was increased in cortical neurons of the peri-infarct regions. Both infarction size and neuronal death in I/R injury were significantly reduced by adeno-associated virus (AAV)-mediated transduction of Nox1 short hairpin RNA (shRNA). AAV-mediated Nox1 knockdown enhanced functional recovery after MCAO. The level of survival and differentiation of newborn cells in the peri-infarct regions were increased by Nox1 inhibition. Our data suggest that Nox-1 may be responsible for oxidative damage to DNA, subsequent cortical neuronal degeneration, functional recovery, and regulation of ischemic neurogenesis in the peri-infarct regions after stroke.
authors.affiliation: Department of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea; Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Korea.
authors.forename: Kyoung-Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Korea.
authors.forename: Hahn-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, United States of America.
authors.forename: Yoon-Seong
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Immunology and Physiology, Functional Genomics Institute, College of Medicine, Konkuk University, Chungju, Korea.
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul, Korea; Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Korea.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001483:Base Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death; D002454:Cell Differentiation; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D058953:Neural Stem Cells / Q000473:pathology; D055495:Neurogenesis; D009474:Neurons / Q000201:enzymology* / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000150:complications; D020521:Stroke / Q000150:complications*; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D004247:DNA; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat