The distribution of aluminum into and out of the brain

The extent, rate and possible mechanism(s) by which aluminum enters and is removed from the brain are presented. Introduction of Al into systemic circ ulation as Al transferrin, the predominant Al species in plasma, resulted i n about 7 x 10(-5) of the dose in the brain 1 day after injection. This bra in Al entry could be mediated by transferrin-receptor-mediated endocytosis (TfR-ME). When Al citrate, the predominant small molecular weight Al specie s in blood plasma, is introduced systemically, Al rapidly enters the brain. The rate of Al citrate brain influx suggests a more rapid process than med iated by diffusion or TW-ME. The question has been raised: "Is the brain a 'one-way sink' for aluminum?". Clinical observations are a basis for this s uggestion. Rat brain Al-26 concentrations decreased only slightly from 1 to 35 days after systemic Al-26 injection, in the absence or presence of the aluminum chelator desferrioxamine, suggesting prolonged brain Al retention. However, studies of brain and blood extracellular Al at steady state, usin g microdialysis, suggest brain Al efflux exceeds influx, suggesting carrier -mediated brain Al efflux. The predominant brain extracellular fluid Al spe cies is probably Al citrate. The hypothesis that brain Al efflux, presumabl y of Al citrate, is mediated by the monocarboxylate transporter was tested and supported. Although some Al that enters the brain is rapidly effluxed, it is suggested that a fraction enters brain compartments within 24 h from which it is only very slowly eliminated. (C) 1999 Elsevier Science Inc. All rights reserved.