title: The distribution of aluminum into and out of the brain.
abstract: The extent, rate and possible mechanism(s) by which aluminum enters and is removed from the brain are presented. Introduction of Al into systemic circulation as Al.transferrin, the predominant Al species in plasma, resulted in about 7 x 10(-5) of the dose in the brain 1 day after injection. This brain Al entry could be mediated by transferrin-receptor-mediated endocytosis (TfR-ME). When Al.citrate, the predominant small molecular weight Al species in blood plasma, is introduced systemically, Al rapidly enters the brain. The rate of Al.citrate brain influx suggests a more rapid process than mediated by diffusion or TfR-ME. The question has been raised: "Is the brain a 'one-way sink' for aluminum?". Clinical observations are a basis for this suggestion. Rat brain 26Al concentrations decreased only slightly from 1 to 35 days after systemic 26Al 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, using microdialysis, suggest brain Al efflux exceeds influx, suggesting carrier-mediated brain Al efflux. The predominant brain extracellular fluid Al species is probably Al.citrate. The hypothesis that brain Al efflux, presumably 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.
authors.affiliation: College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA. ryokel1@pop.uky.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Yokel
authors.forename: D D
authors.initials: DD
authors.lastname: Allen
authors.forename: D C
authors.initials: DC
authors.lastname: Ackley
mesh_terms: D000535:Aluminum / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D051381:Rats
chemical_list: D000535:Aluminum