{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:17:38Z","timestamp":1790871458693,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,1,12]],"date-time":"2007-01-12T00:00:00Z","timestamp":1168560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p>Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood\u2013brain barrier endothelium, in lesional and normal\u2010appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical grey matter in PPMS and SPMS. Immunocytochemistry and semiquantitative confocal microscopy for the tight junction protein zonula occludens 1 (ZO\u20101) was performed on snap\u2010frozen sections from PPMS (<jats:italic>n<\/jats:italic>\u2003=\u20036) and controls (<jats:italic>n<\/jats:italic>\u2003=\u20035). Data on 2103 blood vessels were acquired from active lesions (<jats:italic>n<\/jats:italic>\u2003=\u200310), inactive lesions (<jats:italic>n<\/jats:italic>\u2003=\u200315), NAWM (<jats:italic>n<\/jats:italic>\u2003=\u200342) and controls (<jats:italic>n<\/jats:italic>\u2003=\u200320). Data on 1218 vessels were acquired from normal\u2010appearing grey matter (PPMS, 5; SPMS, 6; controls, 5). In PPMS abnormal ZO\u20101 expression in active white matter lesions and NAWM, was found in 42% and 13% of blood vessels, respectively, comparable to previous data from acute and SPMS. In chronic white matter plaques, however, abnormalities were considerably more frequent (37%) in PPMS than in SPMS. Abnormality was also more frequent in normal\u2010appearing grey matter in SPMS (23%) than in PPMS (10%). In summary, abnormal tight junctions in both SPMS and PPMS are most frequent in active white matter lesions but persist in inactive lesions, particularly in PPMS. Abnormal tight junctions are also common in normal\u2010appearing grey matter in SPMS. Persistent endothelial abnormality with leak (PEAL) is therefore widespread but variably expressed in MS and may contribute to disease progression.<\/jats:p>","DOI":"10.1111\/j.1365-2990.2006.00781.x","type":"journal-article","created":{"date-parts":[[2007,1,13]],"date-time":"2007-01-13T18:23:47Z","timestamp":1168712627000},"page":"86-98","source":"Crossref","is-referenced-by-count":125,"title":["Persistent endothelial abnormalities and blood\u2013brain barrier leak in primary and secondary progressive multiple 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