TRANSPORT OF IRON IN THE BLOOD-BRAIN-CEREBROSPINAL FLUID SYSTEM

Iron is an important constituent in brain and, in certain regions, e.g ., the basal nuclei, reaches concentrations equivalent to those in liv er. It has a role in electron transfer and is a cofactor for certain e nzymes, including those involved in catecholamine and myelin synthesis . Iron in CSF is likely to be representative of that in interstitial f luid of brain. Transferrin in CSF is fully saturated, and the excess i ron may be loosely bound as Fe(II). Brain iron is regulated in iron de pletion, suggesting a role for the blood-brain barrier (BBB). Iron cro sses the luminal membrane of the capillary endothelium by receptor-med iated endocytosis of ferric transferrin. This results in an initial li near uptake of radioactive iron into brain al an average rate relative to serum of about 3.3 x 10(-3) ml.g of brain(-1).h(-1) in the adult r at. This corresponds to about 80 nmol.kg(-1).h(-1). Much higher rates occur in the postnatal rat. These increase during the first 15 days of life and decline thereafter. Within the endothelium, most of the iron is separated from transferrin, presumably by the general mechanism of acidification within the endosome. Iron appears to be absorbed from t he vesicular system into cytoplasm and transported across the ablumina l plasma membrane into interstitial fluid as one or more species of lo w molecular weight. There is some evidence that ionic Fe(ll) is involv ed. Certainly Fe(ll) ions presented on the luminal side rapidly cross the complete BBB, i.e., luminal and abluminal membranes. Within inters titial fluid, transported iron will bind with any unsaturated transfer rin synthesized or transported into the brain-CSF system. Oligodendroc ytes are one site of synthesis. From interstitial fluid, ferric transf errin is taken up by neurones and glial cells by the usual receptor-me diated endocytosis. Calculations of the amount of iron leaving the sys tem with the bulk flow of CSF indicate that most iron entering brain a cross the capillary endothelium finally leaves the system with the bul k outflow of CSF through arachnoid villi and other channels. A system in which influx of iron into brain is by regulated receptor-mediated t ransport and in which efflux is by bulk flow is ideal for homeostasis of brain iron.