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 iro
n in the endothelial cells was manifest already from E14, declined fro
m P3 to P5, and was almost absent on P10-P15. The choroid plexus epith
elial cells of either ventricle was non-heme iron-containing from E14.
Non-heme iron-containing macrophages situated in the stroma of the ch
oroid plexus were also observed from E14. From E19, the macrophage-lik
e cells tended to invade into (a) regions with transitory structures l
ike the intermediate zone of the cerebral hemisphere, (b) developing a
xonal tracts like corpus callosum and internal capsule, and (c) deep l
ayers of the tectum, a region with an extensive degree of naturally oc
curring cell death. The amoeboid macrophage-like cells observed in the
brain parenchyma gradually acquired prolonged extensions and apparent
ly differentiated into ramified microglia-like cells, which later lost
their non-heme iron-content. Thus, at P70, non-heme iron-positive mic
roglia-like cells were hardly seen reflecting the transitory event of
non-heme iron in microglia-like cells. At P200, non-heme iron-containi
ng microglia cells and oligodendrocytes appeared in manifestly higher
number than at P70, a phenomenon probably related to aging. These resu
lts delineate for the first time the appearance of iron in the develop
ing brain. The results are of relevance for understanding the potentia
l of iron-deficiency for harming the developing central nervous system
, generally by decreased transport of iron through brain capillaries a
nd choroid plexus, and specifically by an impaired modulation of the d
eveloping brain parenchyma by iron-containing macrophages.