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

Abstract

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.

Microglial reaction induced by noncytotoxic methylmercury treatment leads to neuroprotection via interactions with astrocytes and IL‐6 release

“…Moreover, clusters of microglial cells were observed at low, noncytotoxic MeHgCl concentrations in 3D cell cultures (Monnet-Tschudi et al, 1996), whereas it occurred only at cytotoxic MeHgCl concentration in purified microglial cell cultures. Such changes in sensitivity to a neurotoxicant have already been described in different cell culture systems, when cultures of one cell type were compared to mixed cell cultures (Wu and Tiffany-Castiglioni, 1987;Gebhart and Goldstein, 1988;Zurich et al, 1998;Mateu et al, 2000;Katsuki et al, 2001) Taken together, the present results indicate that the microglial activation observed in 3D brain cell cultures after noncytotoxic treatment with MeHgCl may be due at least in part to a direct effect of MeHgCl on microglial cells. Clusters of activated microglial cells, formed in response to MeHgCl in a histotypic environment, may interact with neighboring astrocytes, leading to a local increase of IL-6.…”

Glial fibrillary acidic protein and RNA expression in adult rat hippocampus following low-level lead exposure during development

“…This is in line with a previous study of Selvin-Testa et al (1991), who also showed an increase of GFAP immunoreactivity following early postnatal lead exposure. Reactive gliosis following lead exposure is not a primary reaction of astrocytes to the toxin; in cultures of both immature and mature astrocytes, lead exposure did not induce a reactive gliosis (Holtzman et al 1987;Gebhart and Goldstein 1988;Tiffany-Castiglioni et al 1989;Tiffany-Castiglioni 1993). The primary response of astrocytes to lead is characterized by uptake and storage of the heavy metal intracellularly (Holtzman et al 1982(Holtzman et al , 1987TiffanyCastiglioni et al 1986).…”

Methylmercury Retards the Repair of Wounded Monolayer of Human Brain Microvascular Endothelial Cells by Inhibiting Their Proliferation without Nonspecific Cell Damage

“…10) Lead-a well-known neurotoxic heavy metal-induces cerebral edema and cerebellar hemorrhage via a dysfunction of the blood-brain barrier in the brain of exposed humans and animals, [10][11][12][13] suggesting that the abnormality of blood vessels may cause secondary degeneration of the neurons. Although a similar mechanism is possible in the pathogenesis of MeHg-induced neuropathy in the brain, the toxicity of MeHg to blood vessels has been unclear.…”