The effect of pentylenetetrazole-induced seizures on blood-brain barrier integrity in a rat model of preeclampsia

Abstract

The pathophysiological mechanisms underlying blood-brain barrier (BBB) disruption in preeclampsia/eclampsia have not been elucidated. This study investigated the effect of pentylenetetrazole (PTZ)-induced seizures on the functional and structural properties of the BBB during N (omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension and proteinuria in pregnant rats. Animals were treated with L-NAME for 10 days, beginning on day 10 of pregnancy. The BBB permeability was determined by measurements of sodium fluorescein (NaFlu) extravasation into the brain. Occludin and aquaporin (AQP)-4 immunoreactivities were evaluated in brain sections. Severe proteinuria and significantly increased arterial blood pressure were observed following L-NAME treatment. PTZ-induced seizures in pregnant rats treated with L-NAME increased NaFlu levels in all of the brain regions analyzed (P < 0.01). A significant increase in the extravasation of NaFlu was also observed in the diencephalon of intact pregnant rats treated with PTZ. PTZ-induced seizures in both L-NAME-treated and untreated pregnant rats significantly decreased occludin immunoreactivity in the hippocampal capillaries. L-NAME administration significantly increased AQP-4 immunoreactivity in the astrocytic endfeet surrounding the parietal cortex microvessels of PTZ-treated and untreated pregnant rats. These findings suggest that PTZ-induced seizures lead to a severe disruption of the BBB in preeclampsia and that the paracellular pathway may play an important role in increased BBB permeability in this context.