Journal
JOURNAL OF NEUROCHEMISTRY
Volume 88, Issue 4, Pages 813-820Publisher
WILEY
DOI: 10.1046/j.1471-4159.2003.02221.x
Keywords
blood-brain barrier; cerebrospinal fluid; choroid plexus; free iron; transferrin-bound iron; transport
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Funding
- NIA NIH HHS [AG16223] Funding Source: Medline
- NIEHS NIH HHS [R56 ES008146, ES08146-04, R01 ES008146] Funding Source: Medline
- NINDS NIH HHS [R37 NS034467, R01 NS034467, NS34467] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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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 Fe-59 (1 nM) at rates of 136 +/- 26 and 182 +/- 23 muL/g/min, respectively, while their respective transport rates into brain parenchyma were 1.68 +/- 0.56 and 1.52 +/- 0.48 muL/g/min. Regional Tf receptor density (B-max) in brain endothelium determined with I-125-holo-Tf correlated well with Fe-59-Tf regional brain uptake rates reflecting significant vascular association of iron. Tf-bound and free circulating Fe-59 were sequestered by the choroid plexus and transported into the CSF at low rates of 0.17 +/- 0.01 and 0.09 +/- 0.02 muL/min/g, respectively, consistent with a 10-fold brain-CSF concentration gradient for Fe-59, 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.
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