Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.
An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the permeability of the BBB model, as indicated by the decrease of the transendothelial electrical resistance (TEER). Moreover, as shown by both immunofluorescence and Western blot analyses, BBB breaking is accompanied by a decrease of the synthesis as well as the peripheral localization of occludin, a structural protein of the tight junctions that are responsible for BBB properties.
Proia
Patrizia
P
Dipartimento di Studi Giuridici, Economici, Biomedici, Psicosociopedagogici delle Scienze Motorie e Sportive, Università degli Studi di Palermo, Palermo, Italy.
Schiera
Gabriella
G
Salemi
Giuseppe
G
Ragonese
Paolo
P
Savettieri
Giovanni
G
Di Liegro
Italia
I
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D016923:Cell Death; D002478:Cells, Cultured; D017097:Electric Impedance; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D008954:Models, Biological; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D062793:Occludin; D051381:Rats; D017208:Rats, Wistar
D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat