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F St'astný

Publications and source records attributed to F St'astný.

11 recordsLinked to original sources
PubMed2003

Morphology and ultrastructure of rat hippocampal formation after i.c.v. administration of N-acetyl-L-aspartyl-L-glutamate.

N-Acetyl-L-aspartyl-L-glutamate (NAAG) is one of the most abundant neuroactive compounds in the mammalian CNS. Our recent observations have suggested that NAAG administered into rat cerebral ventricles can cause neuronal death by apparently excitotoxic mechanisms that can be antagonized by the N-methyl-D-aspartate-receptor blockers and by ligands of metabotropic glutamate receptor of Group II. Therefore, the principal aim of the present study has been to use quantitative morphology, electron microscopy and terminal deoxynucleotidyl transferase-mediated biotin dUTP nick-end labeling to study a dose- and time-dependence as well as regional distribution of neurodegeneration in hippocampi of rats after the intraventricular infusion of 0.25 micromol NAAG/ventricle and of equimolar doses of L-glutamate (L-GLU) and N-acetyl-L-aspartate (NAA), breakdown products of NAAG. The degenerative changes were observed after the infusion of 0.25 and 1.25 micromol of NAAG/ventricle, but not when a dose of 0.05 micromol of NAAG/ventricle was injected into each lateral cerebral ventricle. With a dose of 0.25 micromol of NAAG/ventricle the number of degenerated neurons reached a maximum on the fourth day after the infusion. The neuronal damage following bilateral administration of 0.25 micromol of NAAG/lateral cerebral ventricle exhibited features of a delayed neuronal degeneration, expressed mainly in the layer of dentate granule neurons. The degeneration was characterized on the basis of ultrastructural appearance and DNA-fragmentation. The morphological changes caused by L-glutamate and NAA were much smaller than those observed after the administration of NAAG and displayed a different pattern of regional distribution. The present findings suggest that NAAG can cause a loss of hippocampal neurons in vivo, apparently resulting from the neurotoxicity of NAAG itself.

Animals↗
PubMed2001

Quinolinic acid induces oxidative stress in rat brain synaptosomes.

The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

2-Amino-5-phosphonovalerate↗
PubMed2000

Neurotoxicity of NAAG in vivo is sensitive to NMDA antagonists and mGluR II ligands.

N-Acetyl-aspartyl-glutamate (NAAG), an agonist at Group II metabotropic glutamate receptors (mGluR II), also activates the NMDA-type of ionotropic glutamate receptors and, at high micromolar concentrations, has previously been shown to induce neuronal cell death. In the present study we have morphologically quantified the neurotoxic action of intracerebroventricularly administered NAAG on the hippocampal formation and compared it to the action of the selective endogenous NMDA agonist quinolinic acid. Finally, we examined whether the action of NAAG can be modified by NMDA receptor antagonists and mGluR II ligands. NAAG-induced neurodegeneration was found to be less severe than that induced by quinolinate. It was prevented by inhibitors of NMDA receptors and also by an mGluR II agonist (DCG IV) but not by an mGluR II antagonist (EGlu).

Animals↗
PubMed2000

Quinolinic acid enhances permeability of rat brain microvessels to plasma albumin.

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 nmol/0.25 microl/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.

Animals↗
PubMed1998

Intracerebroventricular administration of quinolinic acid induces a selective decrease of inositol(1,4,5)-trisphosphate receptor in rat brain.

[3H]inositol(1,4,5)-trisphosphate (IP3) binding studies have shown decreased [3H]IP3 binding to brain tissue in several neurodegenerative diseases, including Alzheimer's and Huntington's diseases. In addition, previous results obtained from brains of Alzheimer patients indicated a reduction of IP3-receptor protein correlated to neuronal loss. The neurotoxic effect of the glutamate receptor agonist quinolinic acid (QUIN) was therefore examined with respect to the level of IP3-receptor immunoreactivity in rat brain. Neuronal lesions were estimated with antibodies to marker proteins for striatal medium-sized spiny neurons (dopamine- and cyclic AMP-regulated phosphoprotein, Mr 32,000; DARPP-32), synaptic vesicles (synaptophysin), mitochondria (phosphate-activated glutaminase; PAG) and glial cells (glial fibrillary acidic protein; GFAP). Injection of QUIN into rat neostriatum induced a massive loss of striatal medium-sized spiny neurons, and led to a comparable loss of IP3-receptor and PAG immunoreactivity, suggesting a neuronal localisation of both these proteins. In an effort to induce less pronounced excitotoxic damage, intracerebroventricular infusion of QUIN was performed. Following this lesion, the neostriatum showed a negligible loss of DARPP-32 immunoreactivity (-11+/-5%), but contained only 43+/-3% of IP3-receptor immunoreactivity levels compared to controls. In the hippocampus, cerebellum and entorhinal cortex, the IP3-receptor loss was less pronounced. The decrease in the level of IP3-receptor immunoreactivity appears to be selective with respect to the other proteins studied, and the IP3-receptor thus shows extreme sensitivity to QUIN neurotoxicity in the neostriatum.

Animals↗
PubMed1989

[Experimental injuries of the spinal cord].

The authors present the results of five years' research concerned with experimental injuries of the spinal cord. The authors studied in cats and rabbits four types of problems: 1. the dynamics of injuries of the spinal cord from the morphological and biochemical aspect, in particular the development and shape of the lesion after complete severing of the spinal cord at the L2 level which was performed by 10-second extradural compression of the spinal cord with an artery forceps. 2. The possibility of resection of the destroyed spinal tissue one week after the insult and the development of autodestructive processes after this resection. 3. Resection of the entire vertebra L2 in healthy animals and shortening of the spine by means of an original stabilization apparatus. 4. Resection of the vertebra, resection of the autodestroyed parts of the spinal cord and approximation of the stumps of the spinal cord by shortening the spine. The assembled findings are discussed in conjunction with contemporary research into the reconstruction of spinal functions and possible transplantations of the CNS.

Animals↗