EVIDENCE FOR LOW-MOLECULAR-WEIGHT, NON-TRANSFERRIN-BOUND IRON IN RAT-BRAIN AND CEREBROSPINAL-FLUID

Transferrin (Tf) donates iron (Fe) to the brain by means of receptor-m ediated endocytosis of Tf at the brain banters. As Tf transport throug h the brain barriers is restricted, Pe is probably released into the b rain extracellular compartment as non-Tf-bound iron (NTBI). To evaluat e NTBI in the brain and cerebrospinal fluid (CSF), different aged rats (P15, P20, P56) were injected intravenously with [Fe-59-I-125]Tf foll owed by sampling of CSF and brain tissue, Between 80 and 93% of Fe-59 in CSF was absorbed with anti-Tf and 1 and 5% with anti-ferritin antib odies, The fraction of Fe-59 from CSF passing through a 30,000 molecul ar weight (MW) cutoff filter was ap; proximately 5% (P15), 10% (P20), and 15% (P56). Measurements of Fe and Tf concentrations in CSF of P20 rats revealed that the Fe-binding capacity of Tf was exceeded. In the supernatants of brain homogenates, between 94 and 99% of Fe-59 was abs orbed with anti-Tf and anti-ferritin antibodies. The respective fracti ons of Fe-59 in the supernatants passing through the 30 kD cutoff filt er were 4% (P15), 2% (P20), and 6% (P56), In brain homogenates mixed b efore filtering with desferroxamine (DFO) or nitrilotriacetic acid (NT A) which complex loosely protein-bound Fe and non-protein-bound Fe, th ese Fe-59 fractions were 2-fold higher. The results indicate that NTBI is present extracellularly in CSF and probably in brain interstitium, J. Neurosci. Res. 54:486-494, 1998. (C) 1998 Wiley-Liss, Inc.