A quantitative analysis of oligodendrocytes in multiple sclerosis lesions

Abstract

We studied quantitatively the fate of oligodendrocytes (OGs) during lesion formation in 395 lesion areas from biopsy and autopsy tissue of 113 multiple sclerosis cases. The density of OGs in multiple sclerosis lesions was variable at all stages of demyelinating activity, ranging from nearly complete loss to values exceeding those in the periplaque white matter (range 0-970 OGs/mm2) determine whether there were distinct patterns of OG pathology in different patients, we restricted our analysis to the 56 cases in which the longitudinal extent of the lesion extended from periplaque white matter into the active demyelinating edge and inactive plaque centre. Two major groups of OG pathology were defined by the presence or absence of increased OGs within the lesion. In 70% (39 out of 56) of the cases, OGs were variably reduced during active stages of myelin destruction, but reappeared within inactive or remyelinating areas. In inactive areas, an increased number of OGs expressing proteolipid protein (PLP) mRNA compared with those expressing myelin oligodendrocyte glycoprotein (MOG) suggested these cells may have been derived from the progenitor pool. In the remaining 30% (17 out of 56) of the cases, extensive destruction of myelinating cells at active sites of demyelination was observed, but OGs were absent in inactive plaque areas without remyelination. In all lesions from a given patient the pattern of OG pathology remained consistent. A highly significant negative correlation was observed between number of macrophages in lesions and number of MOG- and PLP mRNA-labelled OGs (MOG: r = -0.32, P < 0.0000118; PLP mRNA: r = -0.23, P < 0.00238). OG density did not correlate with T-cell and plasma cell inflammation, or axonal loss. The profound heterogeneity in extent and topography of OG destruction in active demyelinating lesions suggests that in subsets of multiple sclerosis patients, myelin, mature OGs and possibly OG progenitors are differentially affected.

Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice

“…Our results are also supported by the fact that PLP-expressing oligodendrocytes are considered myelin-forming cells derived from oligodendrocyte precursors. 25 Our results also show a rapid amelioration of EAE after the FGF-II treatment. Although we cannot exclude that this finding may be due to the FGF-II-mediated increase of migration speed of oligodendrocyte precursor cells …”

Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

“…45,46 Many reported histological patterns are reflective of different evolution stages: from acute active plaques with abundant macrophages and myelin breakdown, to active (smoldering) rim lesions with macrophage presence concentrated at the rim, to inactive plaques without myelin breakdown. 4 Recent studies also showed remyelination to be more extensive than previously assumed, 47 giving new impetus to the search for an in vivo marker of repair and calling for new paraclinical markers of how tissue destruction occurs in vivo.…”

Functional Genomic Analysis of Oligodendrocyte Differentiation

“…Furthermore, because these two stages of OL differentiation can be controlled independently, it might be possible under pathophysiological circumstances for the first stage of OL differentiation to occur but for the subsequent stage to be inhibited. This raises the question of whether the failure of remyelination to occur in MS plaques, even when surviving OLs are present and contacting axons (Lucchinetti et al, 1999), could be attributable to such a halt in OL differentiation. Using the specific markers of early and late OL differentiation that we have identified, this possibility can now be tested.…”