title: Overexpression of extracellular superoxide dismutase protects against brain injury induced by chronic hypoxia.
abstract: Extracellular superoxide dismutase (EC-SOD) is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1%) for 10 days (H-KI) and compared to transgenic animals housed in room air (RA-KI), wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT). Overall brain metabolism evaluated by positron emission tomography (PET) showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation.
authors.affiliation: Division of Neonatal-Perinatal Medicine, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Nahla
authors.initials: N
authors.lastname: Zaghloul
authors.affiliation: Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of New York and Lilling Family Research laboratory, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Hardik
authors.initials: H
authors.lastname: Patel
authors.affiliation: Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of New York and Lilling Family Research laboratory, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Champa
authors.initials: C
authors.lastname: Codipilly
authors.affiliation: Laboratory of Memory Disorders, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marambaud
authors.affiliation: Neuroimaging Department, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewey
authors.affiliation: Laboratory of Immune & Neural Networks, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Frattini
authors.affiliation: Laboratory of Immune & Neural Networks, Feinstein Institute for Medical Research, Manhasset, New York, United States of America; Department of Molecular Medicine, Hofstra North Shore LIJ School of Medicine, New York, United States of America.
authors.forename: Patricio T
authors.initials: PT
authors.lastname: Huerta
authors.affiliation: Department of Pathology, NSL-IJ, Manhasset, New York, United States of America.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Nasim
authors.affiliation: Department of Molecular Medicine, Hofstra North Shore LIJ School of Medicine, New York, United States of America; Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of New York and Lilling Family Research laboratory, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Miller
authors.affiliation: Division of Neonatal-Perinatal Medicine, The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, United States of America; Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of New York and Lilling Family Research laboratory, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ahmed
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008867:Microtomy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D049268:Positron-Emission Tomography; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D046509:Tissue Culture Techniques; D019076:Transgenes
chemical_list: C491049:Aif1 protein, mouse; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008263:Macrophage Migration-Inhibitory Factors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse; D019788:Fluorodeoxyglucose F18; D013482:Superoxide Dismutase; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse