Tissue preconditioning may explain concentric lesions in Baló's type of multiple sclerosis.
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 1alpha 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.
Stadelmann
Christine
C
Brain Research Center, Medical University of Vienna, Vienna, Austria.
Ludwin
Sam
S
Tabira
Takeshi
T
Guseo
Andras
A
Lucchinetti
Claudia F
CF
Leel-Ossy
Lorant
L
Ordinario
Artemio T
AT
Brück
Wolfgang
W
Lassmann
Hans
H
D000293:Adolescent; D000328:Adult; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000150:complications; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009836:Oligodendroglia / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C497442:HIF1A protein, human; D018840:HSP70 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II