Role of neuronal NADPH oxidase 1 in the peri-infarct regions after stroke

• Published in: PloS one 2015-01, Vol.10 (1), p.e0116814
• Main Authors: Choi, Dong-Hee, Kim, Ji-Hye, Lee, Kyoung-Hee, Kim, Hahn-Young, Kim, Yoon-Seong, Choi, Wahn Soo, Lee, Jongmin
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Astrocytes - pathology; Base Sequence; Brain; Brain - metabolism; Brain - pathology; Brain - physiopathology; Brain injuries; Brain injury; Brain research; Cell Death; Cell Differentiation; Cell Survival; Cerebral blood flow; Cerebral infarction; Damage; Degeneration; Deoxyguanosine; Deoxyribonucleic acid; Dependovirus - genetics; DNA; DNA - metabolism; DNA damage; Enzymes; Experiments; Gene expression; Gene Expression Regulation, Enzymologic; Gene Knockdown Techniques; Head injuries; Immunoreactivity; Infarction; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - enzymology; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - physiopathology; Injury prevention; Ischemia; Laboratory animals; Male; Medicine; NAD(P)H oxidase; NADH, NADPH Oxidoreductases - deficiency; NADH, NADPH Oxidoreductases - genetics; NADH, NADPH Oxidoreductases - metabolism; NADPH Oxidase 1; Nervous system; Neural Stem Cells - pathology; Neurodegeneration; Neurogenesis; Neurons; Neurons - enzymology; Neurons - pathology; Neurosciences; Occlusion; Oxidase; Oxidases; Oxidation-Reduction; Oxidative Stress; Proteins; Rats; Rats, Wistar; Recovery; Recovery of Function; Reperfusion; Reperfusion Injury - complications; Ribonucleic acid; RNA; RNA-mediated interference; Rodents; Science; Stroke; Stroke - complications; Studies; Superoxide; Superoxides; Superoxides - metabolism; Survival; Systematic review; Traumatic brain injury; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0116814

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.