Iron accumulation in the choroid plexus, ependymal cells and CNS parenchyma in a rat strain with low‐grade haemolysis of fragile macrocytic red blood cells. (29th January 2021)

• Record Type: Journal Article
• Authors: Wimmer, Isabella; Scharler, Cornelia; Kadowaki, Taro; Hillebrand, Sophie; Scheiber‐Mojdehkar, Barbara; Ueda, Shuichi; Bradl, Monika; Berger, Thomas; Lassmann, Hans; Hametner, Simon
• Is Part Of: Brain pathology. Volume 31:Number 2(2021)
• Page Start: 333
• Page End: 345
• Publication Date: 2021-01-29
• Subjects: cerebrospinal fluid -- erythrocyte osmotic fragility -- iron overload -- kidney proximal tubule -- multiple sclerosis -- zitter rat; Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12920
• Languages: English
• ISSNs: 1015-6305

Abstract

Abstract: Iron accumulation in the CNS is associated with many neurological diseases via amplification of inflammation and neurodegeneration. However, experimental studies on iron overload are challenging, since rodents hardly accumulate brain iron in contrast to humans. 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‐classical entry sites for iron into the CNS. Non‐haem iron in formalin‐fixed paraffin‐embedded tissue was detected via DAB‐enhanced Turnbull Blue stainings. CSF iron levels were determined via atomic absorption spectroscopy. Ferroportin and aquaporin‐1 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‐type 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‐grade 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–CSF 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. Abstract : LEWzizi rats present with pronounced choroid plexus iron overload in conjunction with elevated levels of iron and cell‐free haemoglobin in the blood and increased RBC fragility. In several human diseases of diverse aetiologies, a pronounced accumulation of iron in choroid plexuses has already been described. Our study highlights the importance of choroid plexuses as iron entry sites into the CNS and their linkage with peripheral iron loads and alterations in red blood cell biology.