Acute Seizure Susceptibility and Chronic Vascular Malformation in a Developmental Mouse Model of Sturge-Weber Syndrome.

Abstract

Sturge-Weber Syndrome (SWS) is a rare neurovascular disorder caused by a somatic mosaic missense point mutation inresulting in a facial capillary malformation (port-wine birthmark) and abnormal blood vessels in the eye and brain. Symptoms include seizures, stroke-like episodes, and glaucoma. Acute seizures induced with low-dose kainate in a transgenicR183Q mouse model of SWS assessed seizure susceptibility and the impact of seizures on cerebral vasculature. Mice expressing humanmutation experienced more severe seizures and greater seizure-induced mortality compared to littermate controls. Mutant mice had longer cortical microvessels, with larger diameters; the expression of tight junction proteins was reduced 2 days after seizures. Blood-brain barrier permeability was not different from controls after chronic gene expression, although vascular dilation persisted compared to controls. These data demonstrate increased seizure susceptibility in this somatic mosaic model of SWS, bidirectional interactions between seizure and vascular remodeling, and chronic persistence of vascular malformation.