Entry, half-life, and desferrioxamine-accelerated clearance of brain aluminum after a single Al-26 exposure

The objectives of our study were to estimate the percentage of aluminum (Al ) that enters the brain, the half-life of brain Al, an the ability of an Al chelator to reduce brain Al. Rats received an iv infusion of Al transferri n, the primary Al species in plasma, or citrate, the predominant small mole cular weight Al species in plasma. The infusion contained similar to 0.2-0. 3 nCi (0.4-0.6 nmol) Al-26, enabling the study of At distribution into and retention by the brain at physiological Al concentrations. Some Al transfer rin-infused rats received ip injections of the Al chelator desferrioxamine (DFO), 0.15 mmol/kg, three times weekly. The others received saline injecti ons. The rats were euthanized from 4 hr to 4 days (Al citrate) or 256 days (Al transferrin) later. Brain Al-26 was determined by accelerator mass spec trometry. Peak brain Al-26 concentration was similar to 0.005% of the Al-26 dose in each gram of brain, irrespective of Al species administered. In th e absence of DFO treatments, brain Al-26 concentration decreased with a hal f-life of approximately 150 days. The brain Al half-life in the DFO-treated rats was approximately 55 days. The results show a small fraction of Al in blood enters the brain, where it persists for a long time. The ability of repeated DFO treatments to modestly accelerate the reduction of brain Al is consistent with the necessity of prolonged DFO therapy to significantly re duce Al-induced dialysis encephalopathy.