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  • Title: Molecular changes in white matter adjacent to an active demyelinating lesion in early multiple sclerosis.
    Author: Zeis T, Probst A, Steck AJ, Stadelmann C, Brück W, Schaeren-Wiemers N.
    Journal: Brain Pathol; 2009 Jul; 19(3):459-66. PubMed ID: 19016740.
    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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