Item – Theses Canada

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OCLC number
46557738
Author
Noseworthy, Michael D.(Michael David),1965-
Title
Brain oxidative stress following zinc deficiency and hyperoxia exposure.
Degree
Ph. D. -- University of Guelph, 1997
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, 1997.
Description
2 microfiches.
Notes
Includes bibliographical references.
Abstract
Brain oxidative stress was examined using Magnetic Resonance Imaging (MRI) and in vivo Nuclear Magnetic Resonance (NMR) spectroscopy in weanling male Wistar rats. Two forms of brain oxidative stress, relevant to premature infants, were examined. The first was an acute stress involving a 2 minute period of anoxic-anoxia (100% N$\sb2)$ followed by 15 minutes of hyperoxia (100% O$\sb2).$ This mimics potential parturition stress of umbilicus twisting, and subsequent cessation of fetal blood oxgenation, followed by post-partum hyperoxic therapy. The second stress examined was prolonged hyperoxia exposure (85% O$\sb2).$ This mimics fetal postpartum maintenance in an incubator. Brain T2-weighted MR image signal intensity decreased during Model I. Electron spin resonance and in vivo spin trapping with $\alpha$-phenyl-N tert-butylnitrone confirmed the loss of image intensity was free radical mediated. This suggests free radicals may be important in anoxic-anoxia occasionally experienced by infants during parturition. Prolonged hyperoxia resulted in loss of blood-brain barrier (BBB) integrity, as determined non-invasively using gadolinium enhanced dynamic MRI. There was a diffuse increase in BBB permeability (k) and lesion leakage space $(v\sb{leak})$ observed throughout the brain. In addition, in vivo $\sp {31}$P-NMR showed phosphocreatine, adenosine triphosphate, and phosphate diesters significantly increased. Superimposing dietary zinc deficiency on hyperoxia exposure resulted in a further increase in BBB permeability, brain edema, and the apparent inability of the brain to increase high energy phosphates. This may indicate a lack of ability of the zinc deficient brain to adapt to oxidative stress. Biochemically the zinc deficient brain, after hyperoxia exposure, had a higher oxidized to reduced glutathione ratio, increased lipid peroxidation, increased protein thiol group oxidation, and significantly lower zinc content. These biochemical changes may be a reflection of low CuZn superoxide dismutase activity resulting in a subdued ability to reduce superoxide radicals to $\rm H\sb2O\sb2.$ In addition, zinc deficiency results in a subadequate protection of protein thiol groups and lipids resulting in protein, and lipid damage, respectively. From these data it is suggested that premature infants, low in antioxidants such as zinc, may be at risk for free radical mediated brain damage when exposed to prolonged hyperoxia.
ISBN
0612205096
9780612205093