Quinolinic acid enhances permeability of rat brain microvessels to plasma albumin

被引:38
|
作者
St'astny, F
Skultétyová, I
Pliss, L
Jezová, D
机构
[1] Acad Sci Czech Republ, Inst Physiol, Dept Mol Neurobiol, CZ-14220 Prague, Czech Republic
[2] Prague Psychiat Ctr, Dept Brain Pathophysiol, Prague, Czech Republic
[3] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia
关键词
quinolinic acid; blood-brain barrier; plasma albumin extravasation; cerebrospinal fluid; neurodegeneration; AIDS dementia complex;
D O I
10.1016/S0361-9230(00)00368-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Several studies have established that increased cerebrospinal fluid (CSF) levels of quinolinic acid (QUIN), a macrophage/microglia-derived excitotoxin with N-methyl-D-aspartate (NMDA)-receptor affinity, may reflect abnormal blood-brain barrier (BBB) function in patients with acquired immunodeficiency syndrome (AIDS) dementia complex, exhibiting a relationship to their clinical and neurological status, This study was aimed to evaluate whether QUIN (250 nmo1/0.25 mul/ventricle) infused into both lateral cerebral ventricles permeates adult rat brain microvessels to plasma albumin, possible BBB dysfunction was examined 4 days after the intracerebroventricular (i.c.v.) infusion of QUIN by measuring plasma albumin extravasation using rocket immunoelectrophoresis. The i.c.v. infusion of QUIN failed to increase the extracellular tissue concentration of albumin in the entorhinal cortex, but significantly higher levels were found in the hippocampus proper (but not in the subiculum region and dentate gyrus) and in the striatum. To evaluate the possible relationship between plasma protein extravasation and QUIN-induced tissue necrosis, we quantified neuronal death in the rat hippocampal formation (subiculum, CA1/CA3 areas of the hippocampus proper, dentate gyrus), We found significantly higher tissue levels of plasma albumin in the hippocampus 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 which 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 depend 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 levels 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.
引用
收藏
页码:415 / 420
页数:6
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