Oxidative Stress in White Matter Injury
White matter is the region of the brain underlying gray matter and comprises over half the human brain. Its elements, axons, oligodendrocytes (myelin-producing cells), and oligodendroglia progenitor cells, are exceedingly vulnerable to oxidative stress, since axons contain abundant mitochondria (organelles that are a main source of reactive oxygen species), and the myelin sheath contains numerous lipids, which can be peroxidized after oxidative stress. In addition, low levels of reduced glutathione and high levels of iron content in oligodendrocytes and oligodendrocyte progenitors contribute to this vulnerability. White matter is at risk for oxidative ischemic injury throughout life, from periventricular white matter injury in neonates to stroke and vascular dementia in later life. Prevention of oxidative stress could be a clinical strategy for ischemic white matter injury.
KeywordsManganese Glutathione Superoxide Respiration Arginine
Amyloid precursor protein
Endothelium nitric oxide synthase
Inducible nitric oxide synthase
Myelin basic protein
Middle cerebral artery
Neuronal nitric oxide synthase
Nitric oxide synthase
Nicotinamide adenine dinucleotide phosphate oxidase
Periventricular white matter injury
Reactive oxygen species
An antibody against a non-phosphorylated neurofilament epitope
Copper/zinc superoxide dismutase
Manganese superoxide dismutase
We thank Liza Reola and Bernard Calagui for technical assistance.
This work was supported by grants PO1 NS014543, RO1 NS025372, and RO1 NS038653, from the National Institutes of Health, and by the James R. Doty Endowment.
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