Excitotoxicity is a central pathological pathway in many neurological diseases with
blood-brain barrier (BBB) dysfunction. Kainate, an exogenous excitotoxin, induces
epilepsy and BBB damage in animal models, but the direct effect of kainate on brain
endothelial cells has not been studied in detail. Our aim was to examine the direct
effects of kainate on cultured cells of the BBB and to test three anti-inflammatory
and antioxidant drugs used in clinical practice, simvastatin, edaravone and dexamethasone,
to protect against kainate-induced changes.Primary rat brain endothelial cell, pericyte
and astroglia cultures were used to study cell viability by impedance measurement.
BBB permeability was measured on a model made from the co-culture of the three cell
types. The production of nitrogen monoxide and reactive oxygen species was followed
by fluorescent probes. The mRNA expression of kainate receptors and nitric oxide synthases
were studied by PCR.Kainate damaged brain endothelial cells and made the immunostaining
of junctional proteins claudin-5 and zonula occludens-1 discontinuous at the cell
border indicating the opening of the barrier. The permeability of the BBB model for
marker molecules fluorescein and albumin and the production of nitric oxide in brain
endothelial cells were increased by kainate. Simvastatin, edaravone and dexamethasone
protected against the reduced cell viability, increased permeability and the morphological
changes in cellular junctions caused by kainate. Dexamethasone attenuated the elevated
nitric oxide production and decreased the inducible nitric oxide synthase (NOS2/iNOS)
mRNA expression increased by kainate treatment.Kainate directly damaged cultured brain
endothelial cells. Simvastatin, edaravone and dexamethasone protected the BBB model
against kainate-induced changes. Our results confirmed the potential clinical usefulness
of these drugs to attenuate BBB damage.
