A quantitative analysis of oligodendrocytes in multiple sclerosis lesions - A study of 113 cases

We studied quantitatively the fate of oligodendrocytes (OGs) during lesion formation in 395 lesion areas from biopsy and autopsy tissue of 113 multipl e sclerosis cases. The density of OGs in multiple sclerosis lesions was var iable at all stages of demyelinating activity, ranging from nearly complete loss to values exceeding those in the periplaque white matter (range 0-970 OGs/mm(2)). To determine whether there were distinct patterns of OG pathol ogy in different patients, we restricted our analysis to the 56 cases in wh ich the longitudinal extent of the lesion extended from periplaque white ma tter into the active demyelinating edge and inactive plaque centre, Two maj or groups of OG pathology were defined by the presence or absence of increa sed OGs within the lesion, In 70% (39 out of 56) of the cases, OGs were var iably reduced during active stages of myelin destruction, but reappeared wi thin inactive or remyelinating areas. In inactive, areas, an increased numb er of OGs expressing proteolipid protein (PLP) mRNA compared with those exp ressing 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 sit es of demyelination was observed, but OGs were absent in inactive plaque ar eas without remyelination, In all lesions from a given patient the pattern of OG pathology remained consistent, A highly significant negative correlat ion was observed between number of macrophages in lesions and number of MOG - and PLP mRNA-labelled OGs (MOG: p = -0,32, P < 0.0000118; PLP mRNA: r = - 0,23, P < 0,00238), OG density did not correlate with T-cell and plasma cel l inflammation, or axonal loss. The profound heterogeneity in extent and to pography 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.