TY - JOUR
T1 - Tissue preconditioning may explain concentric lesions in Baló's type of multiple sclerosis
AU - Stadelmann, Christine
AU - Ludwin, Sam
AU - Tabira, Takeshi
AU - Guseo, Andras
AU - Lucchinetti, Claudia F.
AU - Leel-Össy, Lorant
AU - Ordinario, Artemio T.
AU - Brück, Wolfgang
AU - Lassmann, Hans
N1 - Funding Information:
We thank Marianne Leiszer and Helene Breitschopf for expert technical assistance. This study was funded by Fond zur Förderung der wissenschaftlichen Forschung, Austria (grant P 16063-B02), the US Multiple Sclerosis Society (grant RG 3051-A-1) and a prize from the Roman, Marga and Marielle Sobek Foundation. C.S. is supported by the Gemeinnützige Hertie-Stiftung and the medical faculty of the University of Göttingen (junior research group).
PY - 2005/5
Y1 - 2005/5
N2 - Lesions of Baló's concentric sclerosis are characterized by alternating layers of myelinated and demyelinated tissue. The reason for concentric demyelination in this variant of multiple sclerosis is unclear. In the present study we investigated the immunopathology in autopsy tissue of 14 patients with acute multiple sclerosis or fulminant exacerbations of chronic multiple sclerosis with Baló-type lesions in the CNS, focusing on the patterns of tissue injury in actively demyelinating lesions. We found that all active concentric lesions followed a pattern of demyelination that bears resemblances to hypoxia-like tissue injury. This was associated with high expression of inducible nitric oxide synthase in macrophages and microglia. At the edge of active lesions and, less consistently, in the outermost layer of preserved myelin, proteins involved in tissue preconditioning, such as hypoxia-inducible factor 1α and heat-shock protein 70, were expressed mainly in oligodendrocytes and to a lesser degree also in astrocytes and macrophages. Due to their neuroprotective effects, the rim of periplaque tissue, where these proteins are expressed, may be resistant to further damage in an expanding lesion and may therefore remain as a layer of preserved myelinated tissue.
AB - Lesions of Baló's concentric sclerosis are characterized by alternating layers of myelinated and demyelinated tissue. The reason for concentric demyelination in this variant of multiple sclerosis is unclear. In the present study we investigated the immunopathology in autopsy tissue of 14 patients with acute multiple sclerosis or fulminant exacerbations of chronic multiple sclerosis with Baló-type lesions in the CNS, focusing on the patterns of tissue injury in actively demyelinating lesions. We found that all active concentric lesions followed a pattern of demyelination that bears resemblances to hypoxia-like tissue injury. This was associated with high expression of inducible nitric oxide synthase in macrophages and microglia. At the edge of active lesions and, less consistently, in the outermost layer of preserved myelin, proteins involved in tissue preconditioning, such as hypoxia-inducible factor 1α and heat-shock protein 70, were expressed mainly in oligodendrocytes and to a lesser degree also in astrocytes and macrophages. Due to their neuroprotective effects, the rim of periplaque tissue, where these proteins are expressed, may be resistant to further damage in an expanding lesion and may therefore remain as a layer of preserved myelinated tissue.
KW - Baló
KW - HIF-1α
KW - Multiple sclerosis
KW - hsp70
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U2 - 10.1093/brain/awh457
DO - 10.1093/brain/awh457
M3 - Article
C2 - 15774507
AN - SCOPUS:18744394057
SN - 0006-8950
VL - 128
SP - 979
EP - 987
JO - Brain
JF - Brain
IS - 5
ER -