Quinolinic acid enhances permeability of rat brain microvessels to plasma albumin

Several studies have established that increased cerebrospinal fluid (CSF) l evels of quinolinic acid (QUIN), a macrophage/microglia-derived excitotoxin with N-methyl-D-aspartate (NMDA)-receptor affinity, may reflect abnormal b lood-brain barrier (BBB) function in patients with acquired immunodeficienc y syndrome (AIDS) dementia complex, exhibiting a relationship to their clin ical and neurological status, This study was aimed to evaluate whether QUIN (250 nmo1/0.25 mul/ventricle) infused into both lateral cerebral ventricle s permeates adult rat brain microvessels to plasma albumin, possible BBB dy sfunction was examined 4 days after the intracerebroventricular (i.c.v.) in fusion of QUIN by measuring plasma albumin extravasation using rocket immun oelectrophoresis. The i.c.v. infusion of QUIN failed to increase the extrac ellular tissue concentration of albumin in the entorhinal cortex, but signi ficantly higher levels were found in the hippocampus proper (but not in the subiculum region and dentate gyrus) and in the striatum. To evaluate the p ossible relationship between plasma protein extravasation and QUIN-induced tissue necrosis, we quantified neuronal death in the rat hippocampal format ion (subiculum, CA1/CA3 areas of the hippocampus proper, dentate gyrus), We found significantly higher tissue levels of plasma albumin in the hippocam pus proper, in which the CA1 area exhibited the highest neuronal loss while the low rate of neuronal death was not accompanied by significant albumin extravasation in the dentate gyrus, However, in case of the subiculum, in w hich the neuronal loss reached comparable values to those in the CA1 area, we did not find significant enhancement of plasma albumin leakage into this area. The regional differences in brain microvascular permeability may dep end on the density of NMDA receptors in the multicellular capillary barrier , but the differences in neuronal death may also reflect an involvement of NMDA receptors in neuronal membranes, We conclude that increased CSF QUIN l evels evoke a dysfunction of the BBB that may only partially be related to sites with pronounced neuronal damage in the rat brain regions susceptible to NMDA-receptor mediated toxicity, (C) 2000 Elsevier Science Inc.