Electron Microscopic and Behavioral Studies in Experimental Lead Encephalopathy

Clasen, Raymond A.; Hoeppner, Thomas J.; Hartmann, John F.; Pandolfi, Sylvia; Clasen, J R

doi:10.1007/978-3-642-70696-7_7

Cited by 6 publications

(22 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro activation of PKC by low level of Pb exposure was also seen in peripheral blood vessels (Chai and Webb, 1988) and in brain extracts (Long et al, 1994). Inasmuch as brain capillaries serve as the target for Pb toxicity (Bradbury and Deane, 1988;Bressler and Goldstein, 1991;Clasen et al, 1973;Laterra et al, 1992;Press, 1985), it is not surprising that alterations in PKC activity by Pb would likely occur in the choroid plexus, for this highly vascularized tissue is a significant brain compartment for Pb sequestration (Zheng, 1996).…”

mentioning

confidence: 99%

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Zhao

Slavkovich

Zheng

1998

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Lead (Pb) exposure reportedly modulates PKC activity in brain endothelial preparations, which may underlie Pb-induced damage at the blood-brain barrier. Our previous work indicates that Pb accumulates in the choroid plexus and causes dysfunction of this blood-cerebrospinal fluid (CSF) barrier. The present studies were undertaken to test the hypothesis that Pb in the choroid plexus may alter PKC activity and thus affect the functions of the blood-CSF barrier. When choroidal epithelial cells in a primary culture were exposed to Pb (10 μM in culture medium), the membrane-bound PKC activity increased by 5.2-fold, while the cytosolic PKC activities decreased, an indication of the induction of PKC translocation by Pb. The effect of Pb on cellular PKC was concentration dependent in the range of 0.1-10 μM. We further evaluated PKC activity of the choroid plexus in rats chronically exposed to Pb in the drinking water (control, 50 or 250 μg Pb/ml) for 30, 60, or 90 days. Two-way analysis of variance revealed a significant age-related decline of PKC activities in both cytosol and membrane of the choroid plexus. However, Pb treatment did not alter plexus PKC activities. In addition, we found that short-term, acute Pb exposure in rats did not significantly change PKC activities nor did it affect the expression of PKC isoenzymes in the choroid plexus. Our results suggest that Pb exposure may promote the translocation of PKC from cytosol to membrane in rat blood-CSF barrier in vitro, but not in vivo.The mammalian blood-cerebrospinal fluid (CSF) barrier resides primarily in the choroid plexus and plays a pivotal role in regulating the chemical stability of the central nervous system (Johanson, 1995;Davson and Segal, 1996). Toxic metals, especially lead (Pb), have been known to accumulate in the choroid plexus (Friedheim et al., 1983;Manton et al., 1984;O'Tuama et al., 1976;Zheng et al., 1991;Zheng, 1996). Our recent work revealed that accumulation of Pb in the choroid plexus is associated with a significant reduction in CSF concentrations of transthyretin (TTR), a major thyroxine-carrying protein in brain (Zheng et al., 1996). We postulated that Pb accumulation in the choroid plexus might also alter key enzymes that are apparently targeted by cellular Pb toxicity, such as the protein kinase C (PKC).

show abstract

mentioning

confidence: 99%

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Zhao

Slavkovich

Zheng

1998

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

show abstract

“…As in humans, the brains of the pups contain edemal fluid in the cerebellum (Pentschew and Garro 1966), white matter of the cerebrum, caudate nucleus, septum and Purkinje cell layer (Clasen et al 1974). There is vacuolation in the cerebellum (Pentschew and Garro 1966) and basal nuclei (Clasen et al 1974). The molecular layer is replete with capillaries made prominent by the proliferation of endo thelial cells with swollen nuclei (Clasen et al 1974).…”

Section: Pathology Central Nervous System (Cns)mentioning

confidence: 96%

“…Neural tissue Cerebral edema is the most consistent finding in the brain of lead-exposed children (Popoff et al 1963, Raimondi et al 1968, Haley 1971, Clasen et al 1974). The edema is caused by the alceraulou in the pcrmsabiilty of the luicrovessels, allowing a protein-rich transudate to leak through the endothelial junctions into the extra-cellular space (Popoff et al 1963, Clasen et al 1974.…”

Section: Pathology Central Nervous System (Cns)mentioning

confidence: 98%

“…Lead encephalopathy has been defined as any brain disorder caused by lead poisoning, including the subclinical cases characterized only by brain structural changes (Clasen et al 1974). Cerebral edema, accompanied by intracranial pressure increase, may be indicated by papilledema^ increasing clumsinesS; freqi.ienf: loss of balance, ataxia, and lethargy.…”

Section: Symptomatologymentioning

confidence: 99%

“…The edema is caused by the alceraulou in the pcrmsabiilty of the luicrovessels, allowing a protein-rich transudate to leak through the endothelial junctions into the extra-cellular space (Popoff et al 1963, Clasen et al 1974. The ensuing tissue hypoxia in turn results in swelling of astrocytes, which take up plasma proteins (Popoff et al 1963, Clasen et al 1974 and in chronic edema there may be necrosis of neurons and glia (Clasen et al 1974). While the cerebral edema is conspicuous, it is the molecular layer of the cerebellum that sustains the greatest damage (Haley 1971).…”

Section: Pathology Central Nervous System (Cns)mentioning

confidence: 99%

See 2 more Smart Citations

Effects of lead on collagen synthesis and renal function in the rat

Rodolfo-Sioson

View full text Add to dashboard Cite

Use of an in vitro system to study the effects of lead on astrocyte-endothelial cell interactions: A model for studying toxic injury to the blood-brain barrier

Gebhart

Goldstein

1988

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

We investigated the effect of inorganic lead on the interaction of immature rat astrocytes and bovine adrenal endothelial cells. The two cell types were cultured alone and in coculture in the presence or absence of lead acetate for up to 1 week. A battery of cell specific markers was used for cell identification. Newborn Sprague-Dawley rat brain astrocytes were more sensitive than bovine adrenal endothelial cells to the cytotoxic effects of 10-50 microM lead acetate, as demonstrated by a decrease in cell number and by the presence of intracellular vacuoles and detached cells. The number of astrocytes decreased to 50% of control after 4 days in culture at a concentration of 10 microM lead. In contrast, a mitogenic effect of lead was observed on the endothelial cells at this concentration, with an increase in cell number to 110% of control. In coculture, the two cell types demonstrated a distinctive cellular organization and the astrocytes were less sensitive to the cytotoxic effects of lead than when they were cultured alone. A lead-enhanced induction of a neural capillary enzyme activity, gamma-GTP, was detected histochemically in the coculture system. These results are consistent with a maturing or differentiating effect of the endothelial cells on the astrocytes, making them less susceptible to lead and mature enough to induce gamma-GTP activity in the endothelial cells.

show abstract

Electron Microscopic and Behavioral Studies in Experimental Lead Encephalopathy

Cited by 6 publications

References 12 publications

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexusin Vitro,but Notin Vivo

Effects of lead on collagen synthesis and renal function in the rat

Use of an in vitro system to study the effects of lead on astrocyte-endothelial cell interactions: A model for studying toxic injury to the blood-brain barrier

Contact Info

Product

Resources

About