title: Evidence for energy-dependent transport of aluminum out of brain extracellular fluid.
abstract: Aluminum (Al) can cause CNS toxicity. The mechanism of its blood-brain barrier (BBB) permeation is poorly understood. In this study, microdialysis was used to determine extracellular fluid (ECF) unbound aluminum distribution between frontal cortex (FC) and blood during steady-state aluminum concentrations. The brain/blood aluminum ratio was determined. Over a 16-fold range of aluminum concentrations (dosed as aluminum citrate), brain/blood aluminum ratios were 0.10-0.15, consistently and significantly < 1. Aluminum diffusion cannot account for these results, suggesting the presence of a carrier that moves aluminum out of brain extracellular fluid. These aluminum brain/blood ratios (BBRs) were not significantly different over the range of concentrations studied, suggesting an inability to saturate the carrier. Brain/blood aluminum ratios obtained with four aluminum-hydroxypyridinones were also significantly < 1 (0.1-0.3), and were generally significantly different among themselves and from the aluminum citrate BBR. Movement of a BBB permeability marker from blood into brain extracellular fluid suggested partial BBB opening. The aluminum BBRs obtained (all << 1), in the presence of a partially opened BBR, suggest an efficient carrier moving aluminum out of brain ECF. Addition of cyanide to the brain microdialysis probe solution significantly increased the Al (citrate) BBR to 1. These results suggest the presence of an efficient, energy-dependent carrier that removes aluminum from brain ECF, either into brain cells or blood.
authors.affiliation: College of Pharmacy, University of Kentucky Medical Center, Lexington 40536-0082, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Allen
authors.forename: C
authors.initials: C
authors.lastname: Orvig
authors.forename: R A
authors.initials: RA
authors.lastname: Yokel
mesh_terms: D000535:Aluminum / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000535:Aluminum