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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 (A\u03b2), including BBB transport and peripheral clearance of A\u03b2, were investigated in rats with collagen-induced arthritis (CIA), an animal model with similarity to clinical and pathological features of human RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CIA was induced in female Lewis rats. In addition to neuroinflammation, the integrity and function of the BBB were examined. The expression of A\u03b2-transporting proteins at brain blood vessels was measured. Blood-to-brain influx and plasma clearance of A\u03b2 were determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 A\u03b2, 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 A\u03b2, significant higher brain influx of A\u03b2 was observed in the hippocampus of CIA rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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 A\u03b2 indicate the imbalanced BBB clearance of A\u03b2 in RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-021-02086-2","type":"journal-article","created":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T09:02:42Z","timestamp":1611997362000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Changes of blood-brain-barrier function and transfer of amyloid beta in rats with collagen-induced arthritis"],"prefix":"10.1186","volume":"18","author":[{"given":"Po-Hsuan","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Hsuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-You","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Chen Jane","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-3507","authenticated-orcid":false,"given":"Chun-Jung","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,30]]},"reference":[{"key":"2086_CR1","doi-asserted-by":"publisher","first-page":"12063","DOI":"10.1073\/pnas.1810553115","volume":"115","author":"KME Andersson","year":"2018","unstructured":"Andersson KME, Was\u00e9n C, Juzokaite L, Leifsdottir L, Erlandsson MC, Silfversw\u00e4rd ST, et al. 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