Choroid plexus protects cerebrospinal fluid against toxic metals.
Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in the CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cystine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.
Zheng
W
W
Department of Pharmacology and Toxicology, University of Arizona, Tucson 86721.
Perry
D F
DF
Nelson
D L
DL
Aposhian
H V
HV
D000818:Animals; D001151:Arsenic / Q000378:metabolism*; D001774:Blood Chemical Analysis; D002104:Cadmium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002831:Choroid Plexus / Q000378:metabolism*; D003545:Cysteine; D004305:Dose-Response Relationship, Drug; D005978:Glutathione; D007854:Lead / Q000378:metabolism*; D008628:Mercury / Q000378:metabolism*; D008668:Metallothionein; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013438:Sulfhydryl Compounds; D002104:Cadmium; D007854:Lead; D010042:Ouabain; D008668:Metallothionein; D000254:Sodium-Potassium-Exchanging ATPase; D008628:Mercury; D005978:Glutathione; D003545:Cysteine; D001151:Arsenic