LEAD POTENTIATES CYTOKINE-MEDIATED AND GLUTAMATE-MEDIATED INCREASES IN PERMEABILITY OF THE BLOOD-BRAIN-BARRIER

We have measured the transendothelial electrical resistance across the blood-brain barrier (BBB) with a microelectrode technique and determi ned the effects of subcutaneous injections (five injections over ten d ays) of lipopolysaccharide (LPS, 100 ng/g), recombinant mouse interleu kin-6 (IL-6, 5 ng/g), and/or inorganic lead (lead, 2.5 5 mu g/g) on th e ion permeability of arterioles in the temporoparietal cortex of anae sthetized mice between 10 and 40 days of age. In controls the electric al resistance increased with age. It was decreased in animals treated with IL-6, but unaffected by lead at the different ages studied. In IL -6 treated mice, repeated neonatal exposure to lead (five injections b etween 2 and 10 days after birth) caused a delay in the increase in ar teriole resistance with age. LPS injections caused a 36% increase in i on permeability of the BBB in twenty-day-old mice, and lead potentiate d this effect of LPS. Intra-arterial injections of glutamate did not a lter vascular resistance, but topical applications of glutamate on the cerebrum caused a reversible decrease in the resistance in mice not t reated with lead, and an irreversible decrease in mice treated with le ad. injections of glutamate in the lumen of arterial vessels in the pa rietal and temporoparietal brain areas of mice pretreated with lead an d LPS, plus a topical application of glutamate, caused depolarization of neurons in the temporoparietal cortex. These results suggest that d isruption of the BBB can allow serum glutamate to penetrate the brain, causing further disruption of the BBB, and that lead irreversibly pot entiates this cascade of harmful events. (C) 1998 Intox Press, Inc.