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Iron: Oxidative Stress and Neurodegeneration

Protein Oxidation and Heme Oxygenase-1 Induction in Porcine White Matter following Intracerebral Infusions of Whole Blood or Plasma

Wagner K.R.a,c,d · Packard B.A.c · Hall C.L.a · Smulian A.G.d · Linke M.J.d · de Courten-Myers G.M.b · Packard L.M.a · Hall N.C.a

Author affiliations

Departments of aNeurology and bPathology and Laboratory Medicine, and cNeuroscience Graduate Program, University of Cincinnati College of Medicine, and dMedical Research Service, Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA

Related Articles for ""

Dev Neurosci 2002;24:154–160

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Article / Publication Details

First-Page Preview
Abstract of Iron: Oxidative Stress and Neurodegeneration

Received: May 01, 2002
Accepted: June 25, 2002
Published online: October 28, 2002
Issue release date: October 2002

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE

Abstract

Spontaneous or traumatic intracerebral hemorrhage (ICH) in the white matter of neonates, children and adults causes significant mortality and morbidity. The detailed biochemical mechanisms through which blood damages white matter are poorly defined. Presently, we tested the hypothesis that ICH induces rapid oxidative stress in white matter. Also, since clot-derived plasma proteins accumulate in white matter after ICH and these proteins can induce oxidative stress in microglia in vitro, we determined whether the blood’s plasma component alone induces oxidative stress. Lastly, since heme oxygenase-1 (HO-1) induction is highly sensitive to oxidative stress, we also examined white matter HO-1 gene expression. We infused either whole blood or plasma (2.5 ml) into the frontal hemispheric white matter of pentobarbital-anesthetized pigs (∼1 kg) over 15 min. We monitored and controlled physiologic variables and froze brains in situ between 1 and 24 h after ICH. White matter oxidative stress was determined by measuring protein carbonyl formation and HO-1 gene expression by RT-PCR. Protein carbonyl formation occurred rapidly in the white matter adjacent to both blood and plasma clots with significant elevations (3- to 4-fold) already 1 h after infusion. This increase remained through the first 24 h. HO-1 mRNA was rapidly induced in white matter with either whole blood or plasma infusions. These results demonstrate that not only whole blood but also its plasma component are capable of rapidly inducing oxidative stress in white matter. This rapid response, possibly in microglial cells, may contribute to white matter damage not only following ICH, but also in pathophysiological states in which blood-brain-barrier permeability to plasma proteins is increased.

© 2002 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Iron: Oxidative Stress and Neurodegeneration

Received: May 01, 2002
Accepted: June 25, 2002
Published online: October 28, 2002
Issue release date: October 2002

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


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