Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early Multiple Sclerosis |
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Authors: | Thomas Zeis, Alfonse Probst, Andreas Johann Steck, Christine Stadelmann, Wolfgang Brü ck, Nicole Schaeren-Wiemers |
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Affiliation: | Neurobiology, Department of Biomedicine and Neurology, University Hospital Basel, Pharmacenter, Basel, Switzerland.; Institute of Neuropathology, University Hospital Basel, Basel, Switzerland.; Institute of Neuropathology, Georg-August-University Göttingen, Göttingen, Germany. |
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Abstract: | A stereotactic biopsy of a 17-year-old woman revealed an active inflammatory demyelinating lesion compatible with pattern III multiple sclerosis (MS) according to Lucchinetti et al . The biopsy included a white matter region distant from the active inflammatory demyelinating lesion with abnormal MRI signal, lacking histopathological signs of demyelination and/or oligodendrocyte apoptosis. Expression analysis of this area revealed a strong up-regulation of neuronal nitric oxide synthase (nNOS). Furthermore, detection of nitrotyrosine provided evidence for reactive nitrogen species (RNS)-mediated damage to oligodendrocytes. Concomitantly, genes involved in neuroprotection against oxidative stress such as heme oxygenase 1 were up-regulated. Even though a single case report, this study shows earliest molecular changes in white matter surrounding an actively demyelinating lesion during the first manifestation of MS, pointing toward a more widespread pathological process. Therapeutic targeting of the identified mechanisms of tissue injury might be crucial to prevent further lesion formation or secondary tissue damage. |
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Keywords: | multiple sclerosis oligodendrocyte pathology oxidative stress white matter injury |
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