Developmental profile of non-heme iron distribution in the rat brain during ontogenesis.

The entry of iron from blood into the developing rat brain was studied by means of non-heme iron-histochemistry. The content of non-heme iron in the endothelial cells was manifest already from E14, declined from P3 to P5, and was almost absent on P10-P15. The choroid plexus epithelial cells of either ventricle was non-heme iron-containing from E14. Non-heme iron-containing macrophages situated in the stroma of the choroid plexus were also observed from E14. From E19, the macrophage-like cells tended to invade into (a) regions with transitory structures like the intermediate zone of the cerebral hemisphere, (b) developing axonal tracts like corpus callosum and internal capsule, and (c) deep layers of the tectum, a region with an extensive degree of naturally occurring cell death. The amoeboid macrophage-like cells observed in the brain parenchyma gradually acquired prolonged extensions and apparently differentiated into ramified microglia-like cells, which later lost their non-heme iron-content. Thus, at P70, non-heme iron-positive microglia-like cells were hardly seen reflecting the transitory event of non-heme iron in microglia-like cells. At P200, non-heme iron-containing microglia cells and oligodendrocytes appeared in manifestly higher number than at P70, a phenomenon probably related to aging. These results delineate for the first time the appearance of iron in the developing brain. The results are of relevance for understanding the potential of iron-deficiency for harming the developing central nervous system, generally by decreased transport of iron through brain capillaries and choroid plexus, and specifically by an impaired modulation of the developing brain parenchyma by iron-containing macrophages.