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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Agrin / genetics
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Agrin / metabolism
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / metabolism
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Amyotrophic Lateral Sclerosis / pathology*
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Animals
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Astrocytes / metabolism
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Astrocytes / pathology
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Biomarkers
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Blood-Brain Barrier / metabolism
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Blood-Brain Barrier / pathology*
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Brain Stem / metabolism
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Brain Stem / pathology*
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Cell Shape
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Disease Models, Animal
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Endothelial Cells / cytology
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Enzyme-Linked Immunosorbent Assay
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Evans Blue
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Hemosiderin / metabolism
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Immunoglobulins / metabolism
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Immunohistochemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Microscopy, Electron
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Occludin
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Transgenic
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Reverse Transcriptase Polymerase Chain Reaction
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Spinal Cord / metabolism
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Spinal Cord / pathology*
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Staining and Labeling
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Superoxide Dismutase / genetics*
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Zonula Occludens-1 Protein
Substances
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Agrin
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Biomarkers
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Immunoglobulins
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Membrane Proteins
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Occludin
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Ocln protein, rat
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Phosphoproteins
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RNA, Messenger
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Tjp1 protein, rat
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Zonula Occludens-1 Protein
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Evans Blue
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Hemosiderin
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Superoxide Dismutase