Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 45, Issue 12, Pages 1729-1737Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2008.09.023
Keywords
Multiple sclerosis; Reactive oxygen species; Oxidative damage; Antioxidant enzymes; Free radicals
Funding
- Stichting Vrienden MS Research, The Netherlands [MS 05-567, MS 05-358c]
- Institute for Clinical and Experimental Neurosciences, VU University Medical Center
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Reactive oxygen species (ROS) and subsequent oxidative damage may contribute to the formation and persistence of multiple sclerosis (MS) lesions by acting on distinct pathological processes. ROS initiate lesion formation by inducing blood-brain barrier disruption, enhance leukocyte migration and myelin phagocytosis, and contribute to lesion persistence by mediating cellular damage to essential biological macromolecules of vulnerable CNS cells. Relatively little is known about which CNS cell types are affected by oxidative injury in MS lesions. Here, we show the presence of extensive oxidative damage to proteins, lipids, and nucleotides occurring in active demyelinating MS lesions, predominantly in reactive astrocytes and myelin-laden macrophages. Oxidative stress can be counteracted by endogenous antioxidant enzymes that confer protection against oxidative damage. Here, we show that antioxidant enzymes, including superoxide dismutase I and 2, catalase, and heme oxygenase 1, are markedly upregulated in active demyelinating MS lesions compared to normal-appearing white matter and white matter tissue from nonneurological control brains. Particularly, hypertrophic astrocytes and myelin-laden macrophages expressed an array of antioxidant enzymes. Enhanced antioxidant enzyme production in inflammatory MS lesions may reflect an adaptive defense mechanism to reduce ROS-induced cellular damage. (C) 2008 Elsevier Inc. All rights reserved.
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