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Evidence for communication of peripheral iron status to cerebrospinal fluid: clinical implications for therapeutic strategy
Fluids and Barriers of the CNS ( IF 5.9 ) Pub Date : 2020-04-16 , DOI: 10.1186/s12987-020-00190-8
James R Connor 1, 2 , Kari Duck 1 , Stephanie Patton 1 , Ian A Simpson 2 , Lynn Marie Trotti 3 , Richard Allen 4 , Christopher J Earley 4 , David Rye 3
Affiliation  

Background Iron is crucial for proper functioning of all organs including the brain. Deficiencies and excess of iron are common and contribute to substantial morbidity and mortality. Whereas iron’s involvement in erythropoiesis drives clinical practice, the guidelines informing interventional strategies for iron repletion in neurological disorders are poorly defined. The objective of this study was to determine if peripheral iron status is communicated to the brain. Methods We used a bi-chamber cell culture model of the blood–brain-barrier to determine transcytosis of iron delivered by transferrin as a metric of iron transport. In the apical chamber (representative of the blood) we placed transferrin complexed with iron 59 and in the basal chamber (representative of the brain) we placed human cerebrospinal fluid. Cerebrospinal fluid (CSF) samples (N = 24) were collected via lumbar puncture. The integrity of the tight junctions were monitored throughout the experiments using RITC-Dextran. Results We demonstrate that iron transport correlates positively with plasma hemoglobin concentrations but not serum ferritin levels. Conclusions The clinical ramifications of these findings are several- fold. They suggest that erythropoietic demands for iron take precedence over brain requirements, and that the metric traditionally considered to be the most specific test reflecting total body iron stores and relied upon to inform treatment decisions– i.e., serum ferritin–may not be the preferred peripheral indicator when attempting to promote brain iron uptake. The future direction of this line of investigation is to identify the factor(s) in the CSF that influence iron transport at the level of the BBB.

中文翻译:

外周铁状态与脑脊液交流的证据:对治疗策略的临床意义

背景铁对于包括大脑在内的所有器官的正常运作至关重要。铁的缺乏和过量很常见,会导致大量的发病率和死亡率。虽然铁参与红细胞生成推动了临床实践,但指导神经系统疾病补铁干预策略的指南定义不明确。这项研究的目的是确定外周铁状态是否会传达到大脑。方法我们使用血脑屏障的双室细胞培养模型来确定转铁蛋白传递的铁的转胞吞作用,作为铁转运的指标。在心尖室(代表血液)中,我们放置了与铁 59 复合的转铁蛋白,在基底室(代表大脑)中,我们放置了人脑脊液。通过腰椎穿刺收集脑脊液 (CSF) 样本 (N = 24)。在整个实验中使用 RITC-葡聚糖监测紧密连接的完整性。结果我们证明铁转运与血浆血红蛋白浓度呈正相关,但与血清铁蛋白水平无关。结论 这些发现的临床后果是多方面的。他们认为,红细胞生成对铁的需求优先于大脑需求,传统上被认为是反映全身铁储备的最具体测试并依赖于告知治疗决策的指标——即血清铁蛋白——可能不是首选的外周指标当试图促进大脑铁吸收时。
更新日期:2020-04-16
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