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Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin‐bound and free iron into the rat brain
Author(s) -
Deane Rashid,
Zheng Wei,
Zlokovic Berislav V.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02221.x
Subject(s) - choroid plexus , parenchyma , transferrin , blood–brain barrier , cerebrospinal fluid , endothelium , interstitial fluid , chemistry , transferrin receptor , central nervous system , biology , biophysics , endocrinology , medicine , pathology , neuroscience
Iron transport into the CNS is still not completely understood. Using a brain perfusion technique in rats, we have shown a significant brain capillary uptake of circulating transferrin (Tf)‐bound and free 59 Fe (1 n m ) at rates of 136 ± 26 and 182 ± 23 μL/g/min, respectively, while their respective transport rates into brain parenchyma were 1.68 ± 0.56 and 1.52 ± 0.48 μL/g/min. Regional Tf receptor density ( B max ) in brain endothelium determined with 125 I‐holo‐Tf correlated well with 59 Fe‐Tf regional brain uptake rates reflecting significant vascular association of iron. Tf‐bound and free circulating 59 Fe were sequestered by the choroid plexus and transported into the CSF at low rates of 0.17 ± 0.01 and 0.09 ± 0.02 μL/min/g, respectively, consistent with a 10‐fold brain‐CSF concentration gradient for 59 Fe, Tf‐bound or free. We conclude that transport of circulating Tf‐bound and free iron could be equally important for its delivery to the CNS. Moreover, data suggest that entry of Tf‐bound and free iron into the CNS is determined by (i) its initial sequestration by brain capillaries and choroid plexus, and (ii) subsequent controlled and slow release from vascular structures into brain interstitial fluid and CSF.