6533b830fe1ef96bd1297d12
RESEARCH PRODUCT
Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.
Paolo RagoneseGiovanni SavettieriGabriella SchieraPatrizia ProiaItalia Di LiegroGiuseppe Salemisubject
Pathologymedicine.medical_specialtyProgrammed cell deathBlotting WesternBiologyImmunofluorescenceOccludinModels BiologicalMyelinWestern blotOccludinGeneticsmedicineElectric ImpedanceAnimalsmultiple sclerosis brain cell cultures in vitro models of blood-brain barrier neuronal cell death transendothelial electrical resistanceMicroscopy Phase-ContrastRats WistarCells CulturedNeuronsmedicine.diagnostic_testTight junctionCell DeathMultiple sclerosisMembrane ProteinsGeneral MedicineMultiple Sclerosis Chronic Progressivemedicine.diseaseImmunohistochemistryRatsBlotmedicine.anatomical_structurenervous systemBlood-Brain BarrierAstrocytescardiovascular systemdescription
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.
year | journal | country | edition | language |
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2009-10-16 | International journal of molecular medicine |