Permeability of the blood-brain barrier to lead.
This review examines the kinetics and possible mechanisms of lead transport into brain across the microvessel endothelium (the blood-brain barrier). Although severe lead poisoning both in neonatal rats and in young children may cause microvessel damage, there is little evidence that there is either damage or even disturbance of specific transport mechanisms at blood leads < 80 micrograms/dl. When 203Pb was continuously infused intravenously into adult rats, radiotracer uptake into different brain regions was linear with time up to 4 hours, reaching spaces in relation 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 compounds, such as L-cysteine. Transport into brain has been further studied during short vascular perfusion of one cerebral hemisphere of the rat with oxygenated and buffered physiological saline. This allows total control of the fluid perfusing the cerebral microvessels. In the absence of organic ligands for lead, 203Pb entered brain very fast, with a space of 9.7 ml/100 g in frontal cortex at one min. The presence of albumin, L-cysteine or EDTA abolished measurable uptake. Experiments designed to reveal a role for the anion exchanger or calcium channels gave negative results. However, the effects of potassium depolarization and of varying pH indicated that the lead species passively entering the endothelium might be PbOH+. Experiments with various metabolic inhibitors, including vanadate, suggested that Pb uptake in the endothelium is mitigated by active back transport of lead into blood by the Ca-ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)
Bradbury
M W
MW
Division of Biomedical Sciences (Physiology), King's College, London.
Deane
R
R
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics*; D007856:Lead Radioisotopes; D010477:Perfusion; D051381:Rats
D007856:Lead Radioisotopes; D007854:Lead