Iron injection restores brain iron and hemoglobin deficits in perinatal copper-deficient rats

Copper (Cu) deficiency during perinatal development in rats is associated with anemia, lower plasma iron (Fe), and brain Fe. Experiments were conducted to inject Fe dextran into Cu-deficient (Cu-) rat pups to attempt to reverse these conditions. Previous work with older Cu- rats did not reverse anemia following Fe injection. Dams began Cu-adequate (Cu+) or Cu- dietary treatments starting at embryonic d 7 and lasting through weaning. In Expt. 1, pups from each dietary treatment were given a single dose of Fe, 20 mg Fe/kg, or saline (S) at postnatal d 11 (P11). Plasma Fe and hemoglobin were higher in the Fe-injected groups at P13. Brain Fe deficit and brain transferrin receptor enhancement were eliminated in the Cu- group injected with Fe compared with Cu-S pups, supporting an association between low plasma Fe and low brain Fe. In Expt. 2, Fe treatment was increased to 45 mg Fe/kg. Four injections were given between P5 and P18 (total dose, 5-7 mg Fe), At P20, Fe concentrations in 4 brain regions (cortex, cerebellum, medulla/pons, and hypothalamus) generally were higher in all groups than in Cu-S pups. At P25, impaired vibrissae-elicited foot placement was evident in Cu-S rats and was not improved by Fe injection. However, at P26, the brain Fe deficit in Cu-S pups was eliminated by Fe injection. Fe injections in Cu- pups raised plasma Fe, brain Fe, and hemoglobin but did not reverse low cytochrome c oxidase or abnormal striatal behavior.