Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain
Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain
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DOI：
10.1046/j.1471-4159.2003.02221.x
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发表时间：
2004-02-01
影响因子：
4.7
通讯作者：
Zlokovic, BV
中科院分区：
文献类型：
--
作者：
Deane, R;Zheng, W;Zlokovic, BV
铁转运到中枢神经系统仍然不是。完全理解在大鼠中使用脑灌注技术，我们已经显示循环转铁蛋白（Tf）结合的和游离Fe-59（1 nM）的显著脑毛细血管摄取率分别为136 +/- 26和182 +/- 23穆尔/g/min，而它们向脑实质的转运速率分别为1.68 ± 0.56和1.52 ± 0.48穆尔/g/min。Tf与Fe-59-Tf区域脑摄取率相关性良好，反映了铁的显著血管相关性。TF结合和游离的循环Fe-59被脉络丛隔离，并分别以0.17 +/- 0.01和0.09 +/- 0.02穆尔/min/g的低速率转运到CSF中，这与Fe-59、TF结合或游离的10倍脑CSF浓度梯度一致。我们的结论是，运输循环TF结合和游离铁可能是同样重要的，其交付到中枢神经系统。此外，数据表明，Tf结合铁和游离铁进入CNS取决于（i）其最初被脑毛细血管和脉络丛隔离，以及（ii）随后从血管结构受控缓慢释放到脑间质液和CSF中。
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.