PERMEABILITY OF THE BLOOD-BRAIN-BARRIER TO LEAD

This review examines the kinetics and possible mechanisms of lead tran sport into brain across the microvessel endothelium (the blood-brain b arrier). Although severe lead poisoning both in neonatal rats and in y oung children may cause microvessel damage, there is little evidence t hat there is either damage or even disturbance of specific transport m echanisms at blood leads < 80 mug/dl. When Pb-203 was continuously inf used intravenously into adult rats, radiotracer uptake into different brain regions was linear with time up to 4 hours, reaching spaces in r elation to plasma of 6.6-8.2 ml/100 g in cerebral tissues at one hour. The concentration of free Pb+ in serum is of the order of 10(-12) M, the majority of lead being bound to protein and to sulfhydryl compound s, such as L-cysteine. Transport into brain has,been further studied d uring short vascular perfusion of one cerebral hemisphere of the rat w ith oxygenated and buffered physiological saline. This allows total co ntrol of the fluid perfusing the cerebral microvessels. In the absence of organic ligands for lead, Pb-203 entered brain very fast, with a s pace of 9.7 ml/100 g in frontal cortex at one min. The presence of alb umin, L-cysteine or EDTA abolished measurable uptake. Experiments desi gned to reveal a role for the anion exchanger or calcium channels gave negative results. However, the effects of potassium depolarization an d of varying pH indicated that the lead species passively entering the endothelium might be PbOH+. Experiments with various metabolic inhibi tors, including vanadate, suggested that Pb uptake in the endothelium is mitigated by active back transport of lead into blood by the Ca-ATP ase pump. Undoubtedly there is a specific mechanism or mechanisms whic h permits ready access of lead to potential neuronal or glial sites fo r its neurotoxicity. (C) 1993 Intox Press, Inc.