Molecular changes in white matter adjacent to an active demyelinating lesion in early multiple sclerosis.
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.
Zeis
Thomas
T
Neurobiology, Department of Biomedicine and Neurology, University Hospital Basel, Pharmacenter, Basel, Switzerland.
Probst
Alfonse
A
Steck
Andreas Johann
AJ
Stadelmann
Christine
C
Brück
Wolfgang
W
Schaeren-Wiemers
Nicole
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D052248:Nitric Oxide Synthase Type I