{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T07:01:42Z","timestamp":1777014102800,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,11]],"date-time":"2013-03-11T00:00:00Z","timestamp":1362960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2013,4]]},"abstract":"Aims<\/jats:title>Prion diseases are characterized by brain deposits of misfolded aggregated protease\u2010resistant prion protein (PrP<\/jats:styled-content>), termed PrPres<\/jats:styled-content>. In humans and animals, PrPres<\/jats:styled-content> is found as either disorganized non\u2010amyloid aggregates or organized amyloid fibrils. Both PrPres<\/jats:styled-content> forms are found in extracellular spaces of the brain. Thus, both might block drainage of brain interstitial fluid (ISF<\/jats:styled-content>). The present experiments studied whether ISF<\/jats:styled-content> blockage occurred during amyloid and\/or non\u2010amyloid prion diseases.<\/jats:p><\/jats:sec>Methods<\/jats:title>Various\u2010sized fluorescein\u2010labelled ISF<\/jats:styled-content> tracers were stereotactically inoculated into the striatum of adult mice. At times from 5\u2009min to 77\u2009h, uninfected and scrapie\u2010infected mice were compared. C57BL<\/jats:styled-content>\/10 mice expressing wild\u2010type anchored PrP<\/jats:styled-content>, which develop non\u2010amyloid PrPres<\/jats:styled-content> similar to humans with sporadic C<\/jats:styled-content>reutzfeldt\u2013J<\/jats:styled-content>akob disease, were compared with Tg<\/jats:styled-content>44+\/+ mice (transgenic mice secreting anchorless PrP<\/jats:styled-content>) expressing anchorless PrP<\/jats:styled-content>, which develop amyloid PrPres<\/jats:styled-content> similar to certain human familial prion diseases.<\/jats:p><\/jats:sec>Results<\/jats:title>In C57BL<\/jats:styled-content>\/10 mice, extensive non\u2010amyloid PrPres<\/jats:styled-content> aggregate deposition was not associated with abnormal clearance kinetics of tracers. In contrast, scrapie\u2010infected Tg<\/jats:styled-content>44+\/+ mice showed blockage of tracer clearance and colocalization of tracer with perivascular PrPres<\/jats:styled-content> amyloid.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>As tracer localization and clearance was normal in infected C57BL<\/jats:styled-content>\/10 mice, ISF<\/jats:styled-content> blockage was not an important pathogenic mechanism in this model. Therefore, ISF<\/jats:styled-content> blockage is unlikely to be a problem in non\u2010amyloid human prion diseases such as sporadic C<\/jats:styled-content>reutzfeldt\u2013J<\/jats:styled-content>akob disease. In contrast, partial ISF<\/jats:styled-content> blockage appeared to be a possible pathogenic mechanism in Tg<\/jats:styled-content>44+\/+ mice. Thus this mechanism might also influence human amyloid prion diseases where expression of anchorless or mutated PrP<\/jats:styled-content> results in perivascular amyloid PrPres<\/jats:styled-content> deposition and cerebral amyloid angiopathy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2990.2012.01303.x","type":"journal-article","created":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T11:25:17Z","timestamp":1348485917000},"page":"217-230","source":"Crossref","is-referenced-by-count":12,"title":["Non\u2010amyloid and amyloid prion protein deposits in prion\u2010infected mice differ in blockage of interstitial brain fluid"],"prefix":"10.1111","volume":"39","author":[{"given":"A.","family":"Rangel","sequence":"first","affiliation":[{"name":"Laboratory of Persistent Viral Diseases Rocky Mountain Laboratories National Institute of Allergy and Infectious Diseases Hamilton MT 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