Changes of blood-brain-barrier function and transfer of amyloid beta in rats with collagen-induced arthritis

• Published in: Journal of neuroinflammation Vol. 18; no. 1; p. 35
• Main Authors: Lai, Po-Hsuan, Wang, Ting-Hsuan, Zhang, Nai-You, Wu, Kuo-Chen, Yao, Chung-Chen Jane, Lin, Chun-Jung
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.01.2021; BioMed Central; BMC
• Subjects: Alzheimer's disease; Amyloid beta; Animal cognition; Animal models; Antibodies; Arterioles; Arthritis; Biotechnology; Blood vessels; Blood-brain barrier; Brain; Cartilage; Cognitive ability; Collagen; Collagen-induced arthritis; Cytokines; Development and progression; Disease; Fluorescein; Gelatinase B; Genetic aspects; Gliosis; Glycosylation; Government agencies; Hippocampus; Immunization; Inflammation; Intravenous administration; Laboratory animals; Matrix metalloproteinase; Membrane permeability; Metalloproteinase; Neurodegenerative diseases; P-Glycoprotein; Permeability; Protein transport; Proteins; Receptor of advanced glycation end product; Rheumatoid arthritis; Stromelysin 1; Tumor necrosis factor-TNF; Zonula occludens-1 protein; Taiwan; United States > US; P-glycoprotein; Amyloid beta; Blood-brain barrier; Collagen-induced arthritis; Receptor of advanced glycation end product
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-021-02086-2

Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage damage, and systemic inflammation. RA is also associated with the occurrence of neuroinflammation and neurodegenerative diseases. In this study, the impacts of RA on the function of the blood-brain barrier (BBB) and the disposition of amyloid beta (Aβ), including BBB transport and peripheral clearance of Aβ, were investigated in rats with collagen-induced arthritis (CIA), an animal model with similarity to clinical and pathological features of human RA. CIA was induced in female Lewis rats. In addition to neuroinflammation, the integrity and function of the BBB were examined. The expression of Aβ-transporting proteins at brain blood vessels was measured. Blood-to-brain influx and plasma clearance of Aβ were determined. Both microgliosis and astrogliosis were significantly increased in the brain of CIA rats, compared with controls. In terms of BBB function, the BBB permeability of sodium fluorescein, a marker compound for BBB integrity, was significantly increased in CIA rats. Moreover, increased expression of matrix metalloproteinase-3 (MMP-3) and MMP-9 and decreased expression of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were observed in brain microvessels of CIA rats. In related to BBB transport of Aβ, protein expression of the receptor of advanced glycation end product (RAGE) and P-glycoprotein (P-gp) was significantly increased in brain microvessels of CIA rats. Notably, much higher expression of RAGE was identified at the arterioles of the hippocampus of CIA rats. Following an intravenous injection of human Aβ, significant higher brain influx of Aβ was observed in the hippocampus of CIA rats. Neuroinflammation and the changes of BBB function were observed in CIA rats. The increased RAGE expression at cerebral blood vessels and enhanced blood-to-brain influx of Aβ indicate the imbalanced BBB clearance of Aβ in RA.