RATE OF FE-59 UPTAKE INTO BRAIN AND CEREBROSPINAL-FLUID AND THE INFLUENCE THEREON OF ANTIBODIES AGAINST THE TRANSFERRIN RECEPTOR

Uptake of Fe-59 from blood into brains of anaesthetized rats and mice has been studied by intravenous infusion of [Fe-59]ferrous ascorbate or of Fe-59-transferrin, the results not being significantly different. Uptakes in the rat were linear with time, but increased at longer times in the mouse. Transfer constants, K(in) (in ml/g/h x 10(3)), for cerebral hemispheres were 5.2 in the adult rat and 5.6 in the mouse. These K(in) values corresponded to Fe-59 influxes of 145 and 322 pmol/g/h, respectively. Fe-59 uptake into the mouse brain occurred in the following order: cerebellum > brainstem > frontal cerebral cortex > parietal cortex > occipital cortex > hippocampus > caudate nucleus. In genetically hypotransferrinaemic mice, Fe-59 uptake into brain was 80-95 times greater than in To strain mice. Pretreatment of young rats and mice with monoclonal antibodies to transferrin receptors, i.e., the anti-rat immunoglobulin G OX 26 and the anti-mouse immunoglobulin M RI7 208, inhibited Fe-59 uptake into spleen by 94% and 98%, respectively, indicating saturation of receptors. The antibodies reduced Fe-59 uptake into rat brain by 35-60% and that into mouse brain by 65-85%. Although a major portion of iron transport across the blood-brain barrier is normally transferrin-mediated, non-transferrin-bound iron readily crosses it at low serum transferrin levels.