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G Kostopoulos

Publications and source records attributed to G Kostopoulos.

At least 19 recordsLinked to original sources
PubMed2005

Greater contribution of N-methyl-D-aspartic acid receptors in ventral compared to dorsal hippocampal slices in the expression and long-term maintenance of epileptiform activity.

Functional segregation along the dorso-ventral axis of the hippocampus is a developing concept. The higher susceptibility of the ventral hippocampus to epileptic activity compared with dorsal hippocampus is one of the main features, which still has obscure mechanisms. Using the model of magnesium-free medium and field recordings, single epileptiform discharges displayed higher incidence (77% vs 57%), rate (41.7+/-3.1 vs 13.5+/-0.7 events/min), duration (173.9+/-17.7 vs 116.8+/-13.6 ms) and intensity (coastline, 25.4+/-2.5 vs 9.5+/-1.8) in ventral compared with dorsal rat hippocampal slices. In addition, the decay phase of the evoked synaptic potentials was 110% slower in ventral slices. The N-methyl-D-aspartate (NMDA) receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (50-100 microM) decreased the discharge rate and coastline similarly in ventral and dorsal slices, but it shortened the discharges in ventral slices (by 40%) only. The NMDA receptor antagonist 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10 microM) decreased the rate in both groups and additionally shortened discharges in both kinds of slices, an effect which was greater in ventral ones (31% vs 13%). Furthermore, both drugs shortened the evoked potentials more in ventral (77%) than in dorsal slices (52%). On the other hand, 1 microM of 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid shortened the discharges and evoked synaptic potentials only in ventral slices, and slowed down the discharge rate only in dorsal slices. Addition of NMDA, in the magnesium-free medium, enhanced activity in both kinds of slices. At 5 and 10 microM of NMDA 51% of the ventral but only 9% of the dorsal slices displayed persistent epileptiform discharges, which were recorded for at least one hour after reintroduction of magnesium in the medium. At 10-20 microM the enhancement of activity was transient, followed by suppression of discharges in 40% and 76% of the ventral and dorsal slices, respectively. Most of the slices having experienced suppression did not develop persistent activity. We propose that the NMDA receptors contribute to the higher susceptibility of the ventral hippocampus to expression and long-term maintenance of epileptiform discharges. This diversification may be related to other aspects of hippocampal dorso-ventral functional segregation.

2-Amino-5-phosphonovalerate↗
PubMed2003

Vascular network of the rat hippocampus is not homogeneous along the septotemporal axis.

Qualitative and quantitative image analysis of hippocampal vascular bed, after transcardial perfusion of India ink, reveals significant differences among hippocampal subfields and along the septotemporal axis of the rat hippocampus. Ventral hippocampus exhibits significantly higher levels of vascularization compared to dorsal hippocampus, which, however, is characterized by significantly higher capillary density. These results may explain the selective ischemia vulnerability of hippocampus along its septotemporal axis.

Animals↗
PubMed2002

Bronchogenic cyst infected by Salmonella enteritidis followed gastroenteritis.

Congenital bronchogenic cysts of the lung and mediastinum develop from the ventral foregut during embryogenesis. Bronchogenic cysts are seldom seen in the adults and most are thought to be asymptomatic and free of complications unless they become infected or are large enough to cause pressure on contiguous vital structures such as the tracheal carina, the lung or the esophagus. We present the unique case of a 24-year-old man who developed respiratory symptoms after Salmonella enteritidis infected bronchogenic cyst following Salmonella gastroenteritis.

Adult↗
PubMed2000

Dorsal-ventral differentiation of short-term synaptic plasticity in rat CA1 hippocampal region.

Two forms of short-term synaptic plasticity (STP), paired-pulse facilitation (PPF) and frequency potentiation (FP) of CA1 field excitatory postsynaptic potentials (EPSP) to afferent stimulation were compared in slices taken from the dorsal and ventral parts of rat hippocampus. While dorsal slices showed significant PPF at all interpulse intervals (20-1400 ms, 80% at 40 ms), PPF in ventral slices was substantially weaker at intervals shorter than 100 ms (19% at 40 ms) and nil at longer intervals. While dorsal slices showed substantial FP at frequencies 1-40 Hz and frequency depression at 50-100 Hz, ventral slices showed only a much smaller potentiation at 1 Hz and substantial depression at 20-100 Hz. Decreasing [Ca(2+)](o) from 2 to 1 and 0.5 mM substantially reduced the baseline EPSPs in both groups of slices but its effect on PPF was greater in ventral slices. On the contrary when [Ca(2+)](o) was increased to 5 mM only dorsal slices showed an enhancement of baseline EPSP. It is concluded that ventral hippocampus CA1 area has a specific deficit in STP, which is related to the important presynaptic role of calcium and is consistent with a relatively higher transmitter release probability.

Animals↗
PubMed2000

Reduction of A1 adenosine receptors in rat hippocampus after kainic acid-induced limbic seizures.

In a temporal lobe epilepsy (TLE) model induced by kainic acid (KA), we examined the effect of limbic seizures on A1 adenosine receptor distribution in hippocampus and cortex. By using quantitative autoradiography, we determined a progressive decrease in A1 receptor density in CA1 and CA3 regions of hippocampus, which coincided in time with the degenerating process of hippocampal pyramidal cells. This result indicates that a great amount of A1 receptors are located postsynaptically on pyramidal cell dendrites. No difference in A1 receptor density was observed in the inner compared to the outer molecular layer of dentate gyrus, or in the infrapyramidal band compared to the outer layer of stratum oriens of CA3. This could indicate that the newly sprouted mossy fiber glutamatergic terminals do not contain A1 receptors, thus lacking a restrain in the release of glutamate.

Adenosine↗
PubMed2000

Decreased ability of rat temporal hippocampal CA1 region to produce long-term potentiation.

Tetanic stimulation of Schaffer collaterals in the CA1 region of transverse slices, taken from the septal (dorsal) part of young rat hippocampus, produced N-Methyl-D-aspartate-dependent long-term potentiation (LTP) of the rising slope of excitatory postsynaptic potential (mean 38%). Under identical conditions of stimulation (100 Hz, 1 s) slices taken from the temporal (ventral) third of hippocampus presented a substantially reduced ability for LTP (mean 5%). The defect appeared to lie with the induction rather than the maintenance phase of LTP. These results suggest that a significant functional differentiation at the local synaptic plasticity level occurs between the two poles of hippocampus, which together with the substantial differences in their extrinsic connections, may help explain the reported differential participation of neurons in these parts of hippocampus during animal memory tests.

Animals↗
PubMed1998

Lower density of A1 adenosine receptors in nucleus reticularis thalami in rats with genetic absence epilepsy.

The possible involvement of the adenosinergic modulatory system in the pathogenesis of absence seizures was investigated in genetic absence epilepsy rats from Strasbourg (GAERS). Using in vitro quantitative autoradiography, the distribution of A1 adenosine receptors and adenosine uptake sites in the brain of GAERS was studied and compared to that of control animals. An area-specific lower density of A1 receptors (15% decrease) was detected in reticular (nRT) and anterior ventral (AV) thalamic nuclei as well as basal ganglia in the brains of GAERS animals compared with control animals. Since adenosine exerts an anti-oscillatory effect on the thalamic nuclei by suppressing (via A1 receptors) excitatory as well as inhibitory neurotransmitter release, the impairment in A1 receptor density seen here, especially in nRT, could be implicated in the thalamic rhythmicity underlying spike and wave discharges present in this absence epilepsy model.

Adenosine↗
PubMed1998

Development of a transient increase in recurrent inhibition and paired-pulse facilitation in hippocampal CA1 region.

Paired-pulse recurrent inhibition (RI) of population spike (PS) and facilitation (PPF) of field excitatory postsynaptic potential (EPSP) were studied in the CA1 region of hippocampal slices taken from Wistar rats aged from 9 days to 16 months. The comparison of three different paired-pulse protocols revealed the antidromic-orthodromic (A-O) stimulation as the most reliable in quantifying the strength of fast (peaking at 10 ms) and slow (peaking at 200 ms) components of recurrent inhibition. Fast RI, present but weak at 9 days, progressively increased to reach its maximal strength at 30 days, declining in adult (2 m) and middle-aged (16 m) animals. Slow RI was replaced by facilitation at 9 days while it was absent at 15 days. It reached adult values at 30 days. A reduction of the test response at interpulse interval (IPI) of 2-4 ms was strong in developing and adult animals, but was significantly decreased in 16 m. At maximal stimulation PPF was expressed as an enhancement of the slow rather than the fast phase of the EPSP and was particularly strong with a prominent N-methyl-D-aspartate dependent component. A very characteristic selectivity for a prominent PPF at stimulation frequency of 5 Hz appeared first at the 18th day and increased gradually to reach a maximum at the 30th day, after which it declined to very low values in middle-aged animals. A similar developmental pattern was observed in slices taken from rats reared in complete darkness, suggesting a strong innate origin. The ability of hippocampal circuits for plastic gating of information appears to be transiently enhanced at the completion of the first postnatal month as it can be exercised at a wider part of the frequency spectrum, with maximal inhibition and potentiation especially at the frequency of theta rhythm.

Age Factors↗
PubMed1996

Age-related changes in excitability and recurrent inhibition in the rat CA1 hippocampal region.

In hippocampal slices from male Wistar rats aged 1-34 months, we recorded the synaptic field potential responses of the CA1 neurons to stimulation of Schaffer collaterals. Eight electrophysiological indexes were extracted from input/output curves and compared in 11 age groups from 1 to 30 months. Neuronal excitability presented a U-shaped curve of development with a minimum at approximately 7-8 months of age. There was a significant continuous increase in neuronal excitability, i.e. a decrease in excitatory postsynaptic potential (EPSP) producing both the threshold and half-maximal population spike from middle age (8-10 months) to senescence (30 months). Synaptic efficiency also increased in old rats to reach a maximum during senescence, i.e. both the current for threshold EPSP and that for half-maximal EPSP reached a minimum in senescence, although the earlier developmental patterns of these two indexes were non-linear. The duration of the field EPSP elicited with maximal stimulation presented an abrupt decay after the first month. Aged animals presented a relatively small maximal population spike. Recurrent inhibition was most prominent on neuronal excitability rather than synaptic strength. Measured as the percentage change in the half-maximal EPSP and half-maximal population spike, recurrent inhibition was found to decrease during the first 7-10 months of life and remained small in later development.

Age Distribution↗
PubMed1995

Simulation study for the transition from spindles to spike and wave epileptogenesis.

A mathematical model is presented, based on existing anatomical and physiological data, which simulates the behaviour of representative types of cortical cells. It is used to test whether a set of synaptic connections of these cells exists, which, paced by the same rhythmical thalamic input, could produce spindles under normal conditions and spike and wave discharges (SW) under conditions of cortical hyperexcitability. This is possible if the interneurons do not provide recurrent excitatory or inhibitory input on themselves, if the thalamic afferents contact the cortical projecting pyramidal cells through local excitatory neurons, and if the inhibitory interneurons receive input only from the pyramidal cells. The results suggest that an increase of all cortical synaptic actions (both excitatory and inhibitory) is sufficient for the transition from spindles to the first stages in the development of SW discharges in the cortex, whereas the thalamus can be driven to the SW characteristic frequency at the immediate next stages.

Cerebral Cortex↗
PubMed1993

Upregulation of A1 adenosine receptors in human temporal lobe epilepsy: a quantitative autoradiographic study.

A significant increase of A1 adenosine receptor binding (48% increase of mean) was detected in human neocortex obtained from patients suffering from temporal lobe epilepsy as compared to control neocortex from non-epileptic patients. Such increase was equally distributed in the six cortical layers and reached similar levels in each of the five specimens tested independently of age, sex and pharmacological treatment of the patient. Since adenosine exerts a depressant effect on neocortical neurons in slices obtained from epileptic patients, this upregulation of A1 receptor binding may constitute a protective mechanism against subsequent seizures, which is exerted by elevating the depressant response of the brain to endogenous adenosine.

Adenosine↗
PubMed1993

Effect of pentylentetrazol-induced seizures on A1 adenosine receptor regional density in the mouse brain: a quantitative autoradiographic study.

Adenosine has been shown to be a major regulator of neuronal activity in convulsive disorders, exerting its anticonvulsant effect through central A1 adenosine receptors. The aim of the present study was to investigate the effect of generalized tonic-clonic seizures induced by pentylentetrazol on regional changes in A1 adenosine receptor density and distribution in the mouse brain by in vitro quantitative autoradiography. As radioligand the specific agonist of A1 receptors [3H]cyclohexyladenosine was used. After two consecutive (once daily) pentylentetrazol-induced convulsions a widespread upregulation of A1 receptor density was detected with a marked enhancement in structures that mediate seizure activity like hippocampus, mamillary bodies, septum, substantia nigra, thalamic nuclei and cerebral cortices. On the contrary, in basal ganglia a significant downregulation of A1 receptors was observed. These results indicate that: (i) the observed increases or decreases in A1 receptor density are organized in selective anatomical structures related to seizure development rather than uniform in the brain; and (ii) since the upregulation of A1 receptors is sufficient to enhance the physiological depressive response of adenosine, the overall evoked increases seen here may lead to a stronger inhibitory tone and accordingly to a more efficient anticonvulsant effect of endogenous adenosine.

Adenosine↗
PubMed1991

Changes in seizure latency correlate with alterations in A1 adenosine receptor binding during daily repeated pentylentetrazol-induced convulsions in different mouse brain areas.

The seizure latency changed during daily pentylentetrazol (PTZ) induced convulsions showing an increase between days 2 and 4, a rapid decrease between days 5 and 10 and a slight increase again between days 11 and 14. At the respective timepoints, [3H]CHA binding, in cortex and cerebellum of PTZ treated animals followed exactly the same pattern, suggesting that the alterations in A1 receptors in these areas may partly determine the PTZ seizure latency curve. On the contrary, the changes of [3H]CHA binding in hippocampus (sustained increase) and striatum (sustained decrease) didn't follow the latency curve pattern. These results suggest that changes in A1 receptor density in specific brain areas may be involved in the modulation of seizure susceptibility.

Adenosine↗
PubMed1991

Long-term increase in excitability induced by Mg(2+)-free medium in the absence of afferent stimulation in CA1 area of mouse hippocampal slices.

Omission of Mg ions from the perfusion fluid of hippocampal slices unblocks the N-methyl-D-aspartate (NMDA) type of glutamate receptor/channel, and induces long term enhancement of synaptic responses. In order to test the role of afferent activation in induction of long term potentiation in CA1 area by this process, we switched off stimulation during the time of perfusing the slices with Mg(2+)-free medium (30 min). In addition to a short lasting increase in synaptic activation we observed a long term increase in population spike amplitude in all slices tested (n = 5), which lasted for at least 2 h. This process was antagonized by 50-100 microM DL-2-amino-5-phosphonovalerate, a specific NMDA receptor antagonist (n = 8), but not by isolating CA1-CA3 areas prior to the testing (n = 5). These results suggest that the resting levels of the endogenous excitatory neurotransmitter(s) can induce long term increase in firing probability of CA1 pyramidal cells, when NMDA channels are unblocked, in the absence of afferent stimulation and irrespective of CA3 area prior excitation.

2-Amino-5-phosphonovalerate↗
PubMed1991

A comparison of recurrent inhibition and of paired-pulse facilitation in hippocampal slices from normal and genetically epileptic mice.

Tottering mice exhibit inherited generalized epilepsy of the 'absence' type. In hippocampal slices from these mutant mice studied in vitro, pairing an alvear antidromic stimulus to an orthodromic one revealed a strong recurrent inhibition (RI) of CA1 pyramidal neurons. RI was maximal at 10 ms inter-pulse interval (IPI 70% decrease of population spike, PS) gradually decreasing to 15% at 320 ms IPI. At 10 ms IPI it shifted the input/output curves to the right and decreased maximum PS. In the group of slices from epileptic mice the early part of RI (2.5-60 ms) was indistinguishable from that of normal mice, with respect to both its strength and its liability to activity-dependent decrement induced by a train of antidromic stimuli (8 s, 5 Hz). However, the delayed part (80-320 ms) was slightly stronger in the epileptic group. Also in this group only the train of antidromic pulses caused a significant and lasting decrease in the unconditioned orthodromic PS. Paired-pulse facilitation was equally strong in the 2 groups of slices. It is concluded that mechanisms underlying epileptogenic hyperexcitability in the tottering mutant may not include a failure of inhibition, at least in the CA1 area of the hippocampus. On the contrary some inhibitory mechanisms may be stronger.

Animals↗
PubMed1991

Electrophysiological analysis of human neocortex in vitro: experimental techniques and methodological approaches.

In this review we summarize a number of technical and methodological approaches that have been used in our laboratory to study human brain slices maintained in vitro. The findings obtained in the course of these studies appear to be relevant in establishing the mechanisms that underlie physiological phenomena of the human brain such as synaptic plasticity or responses to neuroactive drugs. Moreover, these data are important for understanding certain fundamental mechanisms of epilepsy. In this respect, however, we caution that the mechanisms that apply to different forms of clinical epilepsy might be difficult to find given the variability present in the pathogenesis of human epilepsy.

Cerebral Cortex↗
PubMed1990

Alterations of A1 adenosine receptors in different mouse brain areas after pentylentetrazol-induced seizures, but not in the epileptic mutant mouse 'tottering'.

Single and repeated Pentylentetrazol (PTZ)-induced convulsions are associated with significant changes of A1 adenosine receptors (detected using the radioligand [3H]cyclohexyladenosine, [3H]CHA) in 4 different brain areas of the mouse, namely cortex, hippocampus, cerebellum and striatum. In hippocampus and cerebellum, a rapid increase in [3H]CHA binding, by 26% and 30% respectively, was observed 1 h after a single PTZ convulsion. In striatum, on the contrary, a significant decrease by 30% in [3H]CHA binding was seen, whereas in cortex no significant change could be detected. After daily repeated PTZ convulsions, a significant increase of A1 receptors by 26% appeared also in cortex, while the changes of A1 receptors observed in the other brain areas after a single PTZ convulsion were maintained in almost the same range. All the alterations observed were due to changes of the total number of A1 receptors (Bmax) without changes in receptor affinity (Kd). A significant increase in the latency of PTZ seizure (time between the PTZ-injection and the beginning of the seizure) was also observed after repeated PTZ-induced convulsions at the time when the changes in A1 adenosine receptors were noted. Considered together, these results provide further evidence for an A1 receptor-mediated modulation of seizure susceptibility and indicate that specific brain areas may play different roles in this modulation. The binding of [3H]CHA to membranes from different cortical and subcortical areas of the epileptic mutant mouse 'tottering' was not different from that in control animals.

Adenosine↗