Lead-induced abnormalities in blood-brain barrier permeability in experimental chronic toxicity

Abstract

The aim of this paper was to determine whether prolonged drinking of lead acetate-containing water by adult rats, which imitates environmental exposure to lead (Pb), affects some morphological and biochemical properties of rat brain microvessels. We noted a significant increase of lead level in capillaries and synaptosomes obtained from brains of rats under chronic toxicity conditions. Intravenously injected horseradish peroxidase (HRP) was used to evaluate the functional state of the blood-brain barrier (BBB). The results indicate that, systematically administered at low doses, lead induces BBB dysfunction. The changes, revealed in light microscopy and confirmed by electron microscopic studies, are typical for "leaky" microvessels, reported for variety of neuropathological conditions associated with BBB damage. Enhanced pinocytotic activity of the endothelial cells and the opening of interendothelial tight junctions, together with enormous phagocytizing action of the pericytes, are the most characteristic ultrastructural features noted. The presence of specific type of perivascular cells containing droplets of lipids in the cytoplasm, together with changes in phospholipid profile in brain capillaries, suggest that altered lipid composition of membranes may, at least in part, be responsible for changes in observed membrane permeability.

Molecular targets of lead in brain neurotoxicity

“…Pb 2+ uptake through the blood-brain barrier proceeds at an appreciable rate, consistent with its action as a potent central neurotoxin (Smith et al, 1997). Although severe lead poisoning may compromise the barrier's integrity, and significant abnormalities following Pb 2+ administration have been reported (Struzynska et al, 1997), there is little evidence that l l Pb 2+ can damage the functions of the blood-brain barrier at a dose <80 μg/dl (Bradbury and Deane, 1993), i.e. at doses that mediate chronic or subacute poisoning.…”

Pb2+Inhibition of Sympathetic α7-Nicotinic Acetylcholine Receptor-Mediated Nitrergic Neurogenic Dilation in Porcine Basilar Arteries

“…This, however, is inconsistent with clinical observations that chronic lead exposure increases intracranial pressure (Braun and Gutjahr, 1971;Teo et al, 1997). One possible explanation for the latter findings is that chronic administration of lead may cause blood brain barrier dysfunction (Struzynska et al, 1997), resulting in "leaky" microvessels and increase in membrane permeability.…”

Iron supplement prevents lead-induced disruption of the blood–brain barrier during rat development

“…The high vulnerability of children's brain to Pb toxicity could be partly attributed to the less welldeveloped brain barrier system, or a possibly high sensitivity of their BBB to Pb insults. Evidence has suggested that Pb can directly act on the barrier structure to increase the permeability of the BBB (Bradbury and Deane, 1993;Dyatlov et al, 1998;Kerper and Hinkle, 1997;Press, 1985;Struzynska et al, 1997;Sundstrom et al, 1985). Others have suggested that the growing capillaries may be the primary target to Pb action.…”

“…Children are particularly vulnerable to Pb toxicities for several reasons (Leggett, 1993;Cory-Schlecta and Schaumburg, 2000): they absorb the ingested Pb from the gastrointestinal tract better than do the adults; a greater proportion of systemically circulating Pb gains access to the brain more easily in children, especially those of 5 years old or younger, than in adults; and the developing nervous system in children is far more sensitive to Pb toxicity than the mature adult brains. Evidence in literature also suggests that at low concentrations, Pb disrupts normal blood-brain barrier (BBB) function, resulting in regionally specific increases in permeability to plasma proteins (Dyatlov et al, 1998;Moorhouse et al, 1988;Struzynska et al, 1997;Sundstrom et al, 1985).…”