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Abnormal endothelial tight junctions in active lesions and normal‐appearing white matter in multiple sclerosis
Author(s) -
McQuaid S.,
Plumb J.,
Mirakhur M.,
Kirk J.
Publication year - 2002
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2002.39286_15.x
Subject(s) - occludin , pathology , tight junction , white matter , blood–brain barrier , multiple sclerosis , medicine , infiltration (hvac) , immunofluorescence , vascular permeability , cd68 , confocal microscopy , biology , central nervous system , magnetic resonance imaging , immunohistochemistry , antibody , immunology , materials science , microbiology and biotechnology , radiology , endocrinology , composite material
Increased blood–brain barrier permeability is a feature of new and expanding inflammatory lesions in multiple sclerosis (MS). The pathological mechanism for this increased permeability has not been demonstrated. Materials and methods: Frozen sections from neuropathologically characterized active plaques and normal‐appearing white matter (NAWM) areas in 13 cases of MS were graded according to the relative abundance of oil‐red O (ORO)‐positive cells. Using single and double immunofluorescence and confocal scanning laser microscopy, the tight junction (TJ)‐associated proteins ZO‐1 and occludin were examined in relation to endothelial integrity (Ulex), blood–brain barrier (BBB) leakage (fibrinogen), lymphocytic infiltration and macrophage/microglial activation (HLA‐DR). Blood vessels (10–50 per section) were systematically scanned to acquire image data sets for offline analysis. Results: TJ abnormalities (i.e. beading, interruption or absence of fluorescence, separation or opening of junctions) were frequent (affecting 40% of vessels) in ORO‐positive active plaques, but less frequent in NAWM (<15%) and in normal (2%) and neurological controls (<6%). ‘Open’ junctions were seen both in active ORO‐positive lesions and in inflamed blood vessels in NAWM. Conclusions: These results suggest that disrupted TJs, arising during the acute inflammatory phase of MS, could be responsible for much of the BBB leakage seen in enhancing MRI lesions in vivo.