title: Impaired blood-brain and blood-spinal cord barriers in mutant SOD1-linked ALS rat.
abstract: Blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) impairment is an additional accident occurring during the amyotrophic lateral sclerosis (ALS) progression. In this work, we aimed to decipher if BBB/BSCB leakage appeared before critical detrimental events and could serve as a marker preceding clinical symptoms. Three different BBB leakage markers: Evans blue, IgG and hemosiderin, were used to look at the SOD1-linked ALS rat model at presymptomatic and symptomatic stages. Although IgG and hemosiderin could be detected at presymptomatic stage, Evans blue extravasation which fits best with BBB/BSCB impairment could only be seen at symptomatic stages. BBB/BSCB impairment was further substantiate by showing at symptomatic stages decreased mRNA expression of ZO-1 and occludin as well as agrin, a basal membrane constituent. Electron microscopic data substantiate a toxic environment around endothelial cell and peri-vascular swollen astrocyte end-feet showing oedema-linked BBB opening.
authors.affiliation: Université Libre de Bruxelles, Brussels, Belgium. cnicaise@ulb.ac.be
authors.forename: Charles
authors.initials: C
authors.lastname: Nicaise
authors.forename: Dinko
authors.initials: D
authors.lastname: Mitrecic
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
authors.forename: Robert
authors.initials: R
authors.lastname: De Decker
authors.forename: Michèle
authors.initials: M
authors.lastname: Authelet
authors.forename: Alain
authors.initials: A
authors.lastname: Boom
authors.forename: Roland
authors.initials: R
authors.lastname: Pochet
mesh_terms: D018171:Agrin / Q000235:genetics / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology*; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology*; D048430:Cell Shape; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005070:Evans Blue; D006485:Hemosiderin / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D062793:Occludin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013194:Staining and Labeling; D013482:Superoxide Dismutase / Q000235:genetics*; D062826:Zonula Occludens-1 Protein
chemical_list: D018171:Agrin; D015415:Biomarkers; D007136:Immunoglobulins; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D005070:Evans Blue; D006485:Hemosiderin; D013482:Superoxide Dismutase