Protective effect of glial cells against lipopolysaccharide-mediated blood-brain barrier injury

Numerous infections of the central nervous system are characterized by altered blood-brain barrier (BBB) functions leading to brain damage. To study the mechanisms that cause BBB disruption in these pathologies, we used an in vitro BBB model consisting of a coculture of brain capillary endothelial cells and glial cells. When these endothelial cells were submitted alone to lipopolysaccharide (LPS), added in the luminal compartment, a huge increase in the paracellular permeability of the monolayer was observed. As glial cells surrounding the brain capillaries are of prime importance in specifying at least some cellular properties, we investigated whether glial cells would be able to modulate this endothelial cell response to LPS. When endothelial cells were incubated with LPS added luminally, in the presence of glial cells, LPS surprisingly had no effect on the endothelial cell monolayer permeability, suggesting a protective effect of glial cells on the LPS-mediated injury. As in our experiments, the endotoxin does not interact with the glial cell population. This protective effect suggests a close communication between cerebral endothelial cells and brain parenchymal cells. In our coculture model, the glial cell population is a mixture of astrocytes, oligodendrocytes, and microglial cells. Further experiments performed with purified astrocytes showed that microglial cells or oligodendrocytes, or both, are essential for the complete protection of the endothelial cell monolayer integrity. All these results are direct evidence for a modulatory effect of glial cells on brain capillary endothelial cell response in the pathogenesis of endotoxemia.