Abstract
BackgroundIron 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.MethodsWe 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 iron59 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.ResultsWe demonstrate that iron transport correlates positively with plasma hemoglobin concentrations but not serum ferritin levels.ConclusionsThe 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.
Highlights
Iron is crucial for proper functioning of all organs including the brain
Do those signals occur independent of peripheral iron status? If so, what might guide the clinical decision to prescribe iron supplements for disorders such as Restless Legs Syndrome (RLS) or for enhancement of brain development and function? The goal of this study was to identify relationships between brain iron transport and the traditional peripheral iron metrics serum ferritin that is reflective of systemic iron status or hemoglobin an indicator of red blood cells and oxygen transport capacity of the blood
The samples were combined and interrogated for correlations to serum ferritin and plasma hemoglobin concentrations to determine if peripheral iron status could influence transport of iron at the BBB
Summary
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. Connor et al Fluids Barriers CNS (2020) 17:28 such as restless legs syndrome, and use of iron supplements for children, especially those who have been iron deficient, to promote brain development [7]. It follows that signals from the extracellular fluid in the brain (including CSF) direct the amount of iron that is to be transported across the BBB. Do those signals occur independent of peripheral iron status? What might guide the clinical decision to prescribe iron supplements for disorders such as Restless Legs Syndrome (RLS) or for enhancement of brain development and function? Low serum ferritin levels are thought to reflect low body iron stores and low hemoglobin levels indicate anemia [9]
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