The blood-brain barrier in cortical multiple sclerosis lesions.
The blood-brain barrier (BBB) is composed mainly of specialized endothelial cells characterized by the presence of intercellular tight junctions. Additionally, perivascular cells, astrocytes, and surrounding basement membranes determine BBB integrity. BBB disruption is an early phenomenon in the formation of new white matter multiple sclerosis (MS) lesions; however, knowledge of the extent of BBB changes in gray matter MS lesions is lacking. Here, we studied several markers for BBB integrity in well-characterized brain tissue of patients with MS. Plasma protein leakage was enhanced in white matter lesions compared with that in normal-appearing white matter, whereas plasma protein leakage was absent in gray matter lesions. White matter lesions showed irregular basement membranes and parenchymal depositions of collagen type IV, whereas purely gray matter lesions lacked basement membrane alterations. Similarly, we observed no evidence for astrogliosis and tight junction changes in cortical MS lesions. Although BBB dysfunction is a common feature of white matter MS lesions, cortical MS lesions lack markers for BBB disruption or astrogliosis. Our data may indicate that BBB breakdown is not a critical event in the formation of gray matter MS lesions.
van Horssen
Jack
J
Department of Molecular Cell Biology, VU Medical Center Amsterdam, The Netherlands. j.vanhorssen@vumc.nl
Brink
Bianca P
BP
de Vries
Helga E
HE
van der Valk
Paul
P
Bø
Lars
L
D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D062507:Claudin-5; D024062:Collagen Type V / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D019108:Tight Junctions / Q000473:pathology
C107466:CLDN5 protein, human; D062507:Claudin-5; D024062:Collagen Type V; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D008565:Membrane Proteins; D005340:Fibrinogen