N-Acetyl-l-aspartyl-l-glutamate changes functional and structural properties of rat blood–brain barrier

Abstract

Intracerebroventricular administration of N-acetyl-l-aspartyl-l-glutamate (NAAG), an agonist at group II metabotropic and NR1/NR2D-containing N-methyl-d-aspartate (NMDA) ionotropic glutamate receptors, increased the permeability of the blood–brain barrier (BBB) to serum albumin in the striatum, but produced no similar effects in the entorhinal cortex or in the hippocampal formation. Electron microscopy showed that NAAG, but not its hydrolytic products l-glutamate and N-acetyl-l-aspartate, increased the number of transport vesicles in the hippocampal endothelial cells. Furthermore, immunocytochemistry detected NR2D subunits on hippocampal capillaries. Consequently, NAAG may have influenced the vesicular transport via NMDA receptors. There was, however, no correlation with the regional pattern of BBB changes (increased permeability in the striatum) that, in turn, could not be directly related to the NAAG-induced neurodegeneration described previously in the hippocampus where no significant changes in BBB permeability were detected.