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Here, we studied LEWzizi rats, which present with elevated CNS iron loads, aiming to characterise choroid plexus, ependymal, CSF and CNS parenchymal iron loads in conjunction with altered blood iron parameters and, thus, signifying non\u2010classical entry sites for iron into the CNS. Non\u2010haem iron in formalin\u2010fixed paraffin\u2010embedded tissue was detected via DAB\u2010enhanced Turnbull Blue stainings. CSF iron levels were determined via atomic absorption spectroscopy. Ferroportin and aquaporin\u20101 expression was visualised using immunohistochemistry. The analysis of red blood cell indices and serum\/plasma parameters was based on automated measurements; the fragility of red blood cells was manually determined by the osmotic challenge. Compared with wild\u2010type animals, LEWzizi rats showed strongly increased iron accumulation in choroid plexus epithelial cells as well as in ependymal cells of the ventricle lining. Concurrently, red blood cell macrocytosis, low\u2010grade haemolysis and significant haemoglobin liberation from red blood cells were apparent in the peripheral blood of LEWzizi rats. Interestingly, elevated iron accumulation was also evident in kidney proximal tubules, which share similarities with the blood\u2013CSF barrier. Our data underscore the importance of iron gateways into the CNS other than the classical route across microvessels in the CNS parenchyma. Our findings of pronounced choroid plexus iron overload in conjunction with peripheral iron overload and increased RBC fragility in LEWzizi rats may be seminal for future studies of human diseases, in which similar constellations are found.<\/jats:p>","DOI":"10.1111\/bpa.12920","type":"journal-article","created":{"date-parts":[[2020,11,21]],"date-time":"2020-11-21T20:07:51Z","timestamp":1605989271000},"page":"333-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Iron accumulation in the choroid plexus, ependymal cells and CNS parenchyma in a rat strain with low\u2010grade haemolysis of fragile macrocytic red blood cells"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2231-2120","authenticated-orcid":false,"given":"Isabella","family":"Wimmer","sequence":"first","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"},{"name":"Department 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