Biomedical subjects

S L Erdö

Publications and source records attributed to S L Erdö.

At least 19 recordsLinked to original sources

PubMed1998

Bimoclomol protects against vascular consequences of experimental subarachnoid hemorrhage in rats.

Bimoclomol (BRLP-42) is a novel antiischemic compound acting against peripheral vascular complications of diabetes mellitus (neuropathy, retinopathy, and nephropathy). In the present study the activity of bimoclomol was tested in experimental subarachnoid hemorrhage (SAH) and arachidonic acid (AA)-induced brain edema in rats to elucidate whether the compound may also have beneficial effect in cerebrovascular disturbances. For comparison, a neuroprotective AMPA antagonist, GYKI-52466, was examined. Injury caused by autologous intracranial blood injection or sodium-arachidonate was evaluated by the damage of blood-brain barrier (BBB) reflected in the extravasation of Evans blue dye into the cerebral tissue. Bimoclomol (2 x 2 mg/kg IV) markedly reduced, while GYKI-52466 (2 x 2 mg/kg IV) moderately diminished the extravasation produced by SAH (39.9%, p < 0.01 and 26.7%, p > 0.05, respectively). In the case of AA-induced brain edema, bimoclomol showed less pronounced (19.6%, p < 0.05) inhibitory action, and GYKI-52466 seemed to be more effective (34.2%, p < 0.05). These results suggest that bimoclomol may be active not only in peripheral micro- and macroangiopathy, but also in some types of cerebrovascular disorders.

Animals↗

PubMed1995

Protection against veratridine toxicity in rat cortical cultures: relationship to sodium channel blockade.

Neuroprotection against 100 microM veratridine-induced cell death and inhibition of voltage-dependent sodium currents by phenytoin, carbamazepine, lidocaine and vinpocetine were studied in rat primary cerebrocortical cultures. Neuroprotective efficacies and sodium channel blocking potencies of these drugs failed to show a correlation, suggesting that (i) mechanisms other than sodium channel blockade may be involved in the neuroprotection, and/or (ii) inhibitory efficacy against veratridine- and voltage-activated channels may differ remarkably.

Animals↗

PubMed1995

Vinpocetine is a highly potent neuroprotectant against veratridine-induced cell death in primary cultures of rat cerebral cortex.

The effects of vinpocetine and phenytoin against veratridine-induced cell death were investigated in primary cultures of rat cerebral cortex. Toxicity was evaluated by phase contrast microscopy and quantified by measuring lactic dehydrogenase leakage from damaged cells. Vinpocetine was highly potent in inhibiting the cell death evoked by veratridine. The concentrations of the drug evoking 50% protection (IC50 values) against 100 microM (maximal response) and 50 microM (half-maximal response) veratridine were 490 nM and 63 nM, respectively. The protective efficacy of vinpocetine exceeded about 100-fold that of phenytoin (IC50 = 44.2 microM against 100 microM veratridine), a prototype sodium-channel blocker. These data suggest that the blockade of voltage-gated sodium channels is a possible mechanism of action for the well-known neuroprotective and anticonvulsant properties of vinpocetine.

Animals↗

PubMed1995

Vinpocetine is as potent as phenytoin to block voltage-gated Na+ channels in rat cortical neurons.

The effects of vinpocetine and phenytoin on voltage-gated Na+ channels were examined on cultured cerebrocortical neurones of the rat using a conventional whole-cell patch-clamp method. Vinpocetine and phenytoin decreased Na+ currents in a concentration-dependent manner, with IC50 values of 44.2 +/- 14.6 and 50.5 +/- 17.4 microM, respectively. Both compounds shifted the voltage dependence of the steady-state inactivation of the channel in the hyperpolarising direction. This pronounced Na+ channel blocking activity may contribute to the neuroprotective and anticonvulsant effects of vinpocetine.

Animals↗

PubMed1994

Serum amyloid P component-induced cell death in primary cultures of rat cerebral cortex.

The influence of serum amyloid P component (SAP) on the survival of rat cerebrocortical cultures was tested. Cytotoxic cell death was examined on 8-9-day-old cell cultures by phase contrast microscopy and quantified by the measurement of lactate dehydrogenase (LDH) leakage. SAP (16-48 nM) evoked a concentration-dependent cell death within 24 h exposure. Our results suggest that SAP, as a constituent of cerebral amyloid deposits, may play a role in the pathomechanism of Alzheimer's disease.

Animals↗

PubMed1994

Pronounced increase in prolyl endopeptidase activity in primary cultures of rat cerebral cortex during neuronal differentiation.

The activity of prolyl endopeptidase (PEP), a cytosolic serine protease, was examined in developing primary cultures of the rat cerebral cortex between days 1 and 16, in vitro. Cells underwent remarkable differentiation during the first week in culture, as indicated by the formation of clusters and by the rapid development and fasciculation of neurites. The specific activity of PEP showed a rapid, about 5-fold increase by day 7. The morphology of cultures remained nearly unchanged and the activity of PEP slightly increased during the second week. Excitotoxic lesion of the neuronal component of mature cultures revealed that the majority (over 70%) of PEP activity is localised in glutamate-sensitive neurons. Our findings indicate that PEP may play some role during neuronal differentiation.

Animals↗

PubMed1993

Medium-dependent dissociation of cytotoxic and GABA-releasing effects of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate in rat cortical cultures.

The excitotoxic cell death and the release of gamma-amino-butyric acid (GABA) evoked by excitatory amino acids (EAAs) were comparatively examined in rat cortical sister cultures grown in serum-free (N2) and serum-supplemented (SSM) media. Cell death was induced by 24 h exposure to 1 mM N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) or kainate. [3H]GABA release was evoked by 5 min exposure of preloaded cultures to 0.5 mM NMDA, AMPA or kainate. EAAs evoked remarkable GABA release in both N2 and SSM cultures, but caused toxic cell death in SSM cultures, only. Our findings indicate that functionally active EAA receptors do not necessarily mediate neurotoxicity and suggest that excitotoxicity can be prevented without blocking excitatory transmission.

Animals↗

PubMed1992

The effects of kainate and the glutamate agonist, AMPA, are not separable in rat neocortical cultures.

The excitotoxic and [3H]gamma-aminobutyric acid ([3H]GABA)-releasing effects of quisqualate, alpha-amino-3-hydroxy-4-methyl-5-isoxazolepropionic acid (AMPA), kainate (KA), and their combinations were examined in primary cultures of the rat cerebral cortex. [3H]GABA efflux was evoked by a 5 min exposure of preloaded cultures to the respective agonist(s) (0.5 mM each). Cell death was induced by a 24 h exposure of cells to 1 mM quisqualate, AMPA and/or KA, and was quantified by measuring lactic dehydrogenase leakage. When applied alone, each agonist induced remarkable [3H]GABA release and excitotoxic cell death. Simultaneous administration of AMPA or quisqualate and KA did not evoke stronger responses than KA alone. These results indicate that AMPA and KA receptors are located on the same cortical cells and may activate the same receptor channels and/or intracellular messengers.

Animals↗

PubMed1992

Insulin-specific sensitization of cultured cerebrocortical neurons to glutamate excitotoxicity.

The effect of insulin on the sensitivity of neurons to excitatory amino acid-induced cytotoxic cell death was examined in primary cultures of the rat cerebral cortex. Cells developed for two weeks in serum supplemented medium in the presence or absence of insulin, insulin-like growth factor or b-fibroblast growth factor. Excitotoxic cell death was induced by 1 mmol/l glutamate, N-methyl-D-aspartate, kainate or quisqualate. The vulnerability of cells was evaluated by the measurement of lactate dehydrogenase release due to cytotoxic injury. In contrast to the moderate evaluation of protein content by all the 3 growth factors, only insulin increased the vulnerability of cells to the neurotoxic effects of glutamate and of the 3 excitatory amino acid receptor agonists examined. Our results show that the induction of vulnerability in cortical cultures is a specific action of insulin and not a general effect of growth factors. Moreover, the increased vulnerability to N-methyl-D-aspartate, quisqualate and kainate suggests that the effect of insulin is exerted through intracellular mechanisms other than a selective induction of one subpopulation of excitatory amino acid receptors.

Animals↗

PubMed1992

Developmental dissociation of pharmacological and neurotoxic effects of excitatory amino acids.

The development of excitatory amino acid-(EAA)-induced cytotoxic cell death and [3H]gamma-aminobutyric acid ([3H]GABA) release were simultaneously examined in primary cultures of the rat cerebral cortex. Pronounced [3H]GABA release could already be evoked on day 3 by N-methyl-D-aspartate, quisqualate and kainate, whereas toxic cell death could first be induced on day 7, in vitro. EAA-induced GABA release declined between day 11 and 14, but the excitotoxic vulnerability of cells increased further during the same period. This dissociation of releasing and toxic responses indicates that functionally active EAA receptors do not necessarily mediate excitotoxic effects and suggests that the development of EAA receptors mediating release responses precedes the maturation of intracellular mechanisms involved in excitotoxic neuronal injury, at least in cultured cortical neurons.

Amino Acids↗

PubMed1992

GABA-immunoreactive structures in rat kidney.

We examined the distribution of gamma-aminobutyric acid-like immunoreactivity (GABA-LI) in the rat kidney by light and electron microscopy. In vibratome sections, GABA-LI was present in both the renal medulla and cortex. The inner stripe of the outer medulla was most heavily and almost homogeneously labeled, whereas GABA-LI in the cortex was mainly confined only to some tubules. GABA-positive structures involved the epithelial cells of the thin and the thick ascending limbs of the loop of Henle, the connecting tubules, and the collecting ducts. In GABA-positive connecting tubules and collecting ducts the immunoreactivity was present in the cytoplasm of about half of the epithelial cells. As revealed by electron microscopy, the labeled cells in the collecting tubules were the light (principal) cells. No GABA-LI occurred in neuronal structures. These findings are consistent with the presence of a non-neuronal GABA system in the rat kidney. Furthermore, the specific distribution of GABA in the tubular epithelium suggests a functional significance of this amino acid in tubular transport processes.

Animals↗

PubMed1992

Changes in ligand binding to GABAA receptor sites in pacific salmon (Oncorhynchus) brain during spawning migration and "aging".

When several years old, pacific salmon return to the site of birth, to spawn. At this time, a rapid aging process begins and the fish die within a few weeks after reproducing. Age-related changes of high and low affinity GABA binding sites were studied in salmon brains at three different phases of the spawning migration, i.e. shortly after returning to the natal stream, at the time of spawning, and thereafter. High affinity GABA binding slightly increased while the fish deteriorated. The low affinity component showed a remarkable decrease in density and a concomitant increase in affinity during this final episode of salmon life.

Aging↗

PubMed1991

Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies.

The effect of vinpocetine on excitatory amino acid receptors was examined in the rat brain by two different biochemical approaches. In release experiments with striatal slices, vinpocetine reduced the efflux of dopamine and acetylcholine evoked by glutamate, quisqualate and N-methyl-D-aspartate (NMDA), but not that evoked by kainate. In binding experiments with cortical membranes, vinpocetine reduced the binding of [3H]2-amino-3-3-hydroxy-s-methylisoxasole-4-yl-propionic acid ([3H]AMPA), a quisqualate partial agonist, in an incomplete manner, but failed to influence the binding of [3H]kainate and [3H]3-(2-carboxypyperazine-4-yl)-propyl-1-phosphonic acid ([3H]CPP), an NMDA agonist. These findings suggest that vinpocetine is a quisqualate/AMPA antagonist of some specificity and selectivity.

Acetylcholine↗

PubMed1991

Development of glutamate neurotoxicity in cortical cultures: induction of vulnerability by insulin.

The effect of insulin on the development of excitotoxic vulnerability in primary cultures of the rat cerebral cortex was examined. Cells were maintained for two weeks in serum-supplemented culture media, in the presence or absence of increasing insulin concentrations. Excitotoxic cell death was induced by 1 mM glutamate. The vulnerability of cells was evaluated by phase contrast microscopy and by the measurement of lactate dehydrogenase (LDH) release due to cytotoxic injury. In addition to a moderate (less than 50%) stimulation of protein and DNA synthesis, insulin produced more than a twofold increase in the excitotoxic vulnerability of cells. The effect of insulin was specific, concentration-dependent and required an intact molecular structure of insulin. Our findings indicate that insulin induces significant changes in cerebral neurons by increasing the lethal vulnerability of cortical cells to excitatory amino acids (EAAs).

Animals↗

PubMed1991

Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate.

The capacity of memantine to protect cultured cerebrocortical cells against N-methyl-D-aspartate (NMDA)- and glutamate-induced cell death was examined. Excitotoxic cell death was evaluated by phase contrast microscopy and quantified by estimating the release of lactic dehydrogenase from damaged cells. Memantine showed a strong, long-lasting and concentration-dependent protective effect against the excitotoxic damage induced by glutamate and NMDA, with almost complete protection being attained at a memantine concentration of 0.1 mM. The present findings indicate that memantine has potential value as a drug against excitotoxic brain damage.

Animals↗

PubMed1991

Releasable GABA in tubular epithelium of rat kidney.

The distribution of gamma-aminobutyric acid (GABA) in the rat kidney was examined by immunocytochemical techniques. GABA-like immunoreactivity (GABA-LI) was predominantly confined to the renal tubules, including the ascending parts of the distal tubules, and the loops of Henle, the collecting tubules and ducts, and the connective parts of the convoluted tubules. In GABA-positive cortical tubules, about half of the epithelial cells were labelled. The labelled cell type showed the ultrastructural features of principal cells. Depolarizing stimulation by ouabain and high K+ concentration evoked the efflux of endogenous GABA from kidney slices. The present findings, along with previous results, suggest that GABA released from renal tubular epithelium, and transported with the urine, might be involved in the modulation of contractility in the urinary tract.

Animals↗

PubMed1991

Quisqualate-induced excitotoxic death of glial cells: transient vulnerability of cultured astrocytes.

The cytotoxic effect of quisqualate, a potent excitatory amino acid (EAA), was examined in purified astrocyte cultures obtained from neonatal rat cerebral cortex and grown in a serum-free, defined medium (G5). Excitotoxicity was evaluated by phase contrast microscopy and quantified by the measurement of lactic dehydrogenase (LDH) activity released from the damaged cells into the culture medium. Quisqualate evoked not only osmotic swelling, but also cytotoxic cell death of cultured astrocytes. The vulnerability of cells was restricted to a period between day 4 and 8 in subculture, with a maximal sensitivity on day 7. The present findings indicate that not only neurons, but also glial cells may exhibit excitotoxic vulnerability. The vulnerability to quisqualate appears to be a transient phenomenon, at least in cultured astrocytes.

Animals↗

PubMed1991

Excitatory amino acid receptors in the mammalian periphery.

Aspartate and glutamate occur ubiquitously in free and chemically bound forms and have been considered primarily as substances of metabolic relevance. This focus has changed with the more recent discovery of their specific role as excitatory synaptic transmitters in the mammalian CNS. Enthusiasm for this concept has overshadowed the possibility that glutamate and aspartate may also have specific, receptor-mediated functions in the periphery. In this review, Sándor Erdö summarizes the current knowledge of excitatory amino acid (EAA) receptors outside the CNS, through which EAAs may modulate various functions in peripheral organs and tissues.

Animals↗