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.
MeSH terms
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AMP-Activated Protein Kinases / genetics
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AMP-Activated Protein Kinases / metabolism
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Animals
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Apoptosis
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Biomarkers
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Brain Ischemia / enzymology
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Brain Ischemia / genetics*
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Brain Ischemia / pathology
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Brain Ischemia / prevention & control
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cerebellum / metabolism
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Cerebellum / pathology
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Fluorodeoxyglucose F18 / metabolism
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Gene Expression*
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Glial Fibrillary Acidic Protein
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Hippocampus / metabolism
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Hippocampus / pathology
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Hypothalamus / metabolism
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Hypothalamus / pathology
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Hypoxia / enzymology
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Hypoxia / genetics*
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Hypoxia / pathology
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Hypoxia / prevention & control
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Intramolecular Oxidoreductases / genetics
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Intramolecular Oxidoreductases / metabolism
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Macrophage Migration-Inhibitory Factors / genetics
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Macrophage Migration-Inhibitory Factors / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism
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Microtomy
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Positron-Emission Tomography
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Superoxide Dismutase / genetics*
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Superoxide Dismutase / metabolism
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Tissue Culture Techniques
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Transgenes
Substances
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Aif1 protein, mouse
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Biomarkers
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Calcium-Binding Proteins
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Glial Fibrillary Acidic Protein
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Macrophage Migration-Inhibitory Factors
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Microfilament Proteins
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Nerve Tissue Proteins
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glial fibrillary astrocytic protein, mouse
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Fluorodeoxyglucose F18
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Superoxide Dismutase
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AMP-Activated Protein Kinases
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Caspase 3
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Intramolecular Oxidoreductases
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Mif protein, mouse