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L Velísek

Publications and source records attributed to L Velísek.

At least 19 recordsLinked to original sources
PubMed1995

Resistance of hippocampal synaptic transmission to hypoxia in carbonic anhydrase II-deficient mice.

Mutant Car2n/Car2n mice deficient in carbonic anhydrase II (CA II; a major brain CA isozyme) suffer from systemic acidosis and are more resistant to experimental seizures than their normal littermates (+/+ or +/Car2n). The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor has been shown to contribute to long-term potentiation (LTP) of synaptic transmission, hypoxic/ischemic neuronal injury and to be blocked by extracellular protons (acidosis). We compared the effects of hypoxia on synaptic transmission and LTP in field CA1 of hippocampal slices from CA II-deficient mice to their normal littermates. Slices were subjected to successive 5, 10 and 15 min-periods of hypoxia with 30 min-recovery periods in between. Hippocampal slices from mutant, CA II-deficient mice, were more resistant to all periods of hypoxia tested than slices from normal littermates. In a separate set of mutant and normal slices, there were no differences in LTP of population spike amplitude. The relative resistance of CA II-deficient mice to hypoxia-induced damage may be a consequence of severe interstitial acidosis. The sustained influence of increased extracellular proton concentrations may change the characteristics of NMDA receptors resulting in an increased resistance of synaptic transmission in CA II-deficient mice to hypoxia compared to controls.

Animals↗
PubMed1995

Kainate/AMPA receptor antagonists are anticonvulsant against the tonic hindlimb component of pentylenetetrazol-induced seizures in developing rats.

Non-NMDA receptor antagonists CNQX, DNQX, and NBQX (10-40 mg/kg IP) were tested against pentylenetetrazol-induced (100 mg/kg SC) seizures in 7 to 90-day-old rats. All three drugs significantly decreased the incidence of tonic hindlimb component of tonic-clonic pentylenetetrazol seizures, often in favor of increased incidence of forelimb tonus throughout development. In addition, in 7 to 25-day-old rats, DNQX and NBQX decreased the severity of seizures due to a decrease in total incidence of the tonic component of tonic-clonic seizures compared to age-matched controls. However, neither drug was able to consistently suppress the incidence or increase latency to onset of clonic and tonic-clonic pentylenetetrazol seizures. The data suggest that, during development, non-NMDA receptor transmission may play a role in the generation of the tonic component, but not in the generation of other components of pentylenetetrazol-induced seizures.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Effects of MK-801 and phenytoin on flurothyl-induced seizures during development.

We determined the effects of the N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 15-, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.

Age Factors↗
PubMed1995

Age-dependent effects of gamma-aminobutyric acid agents on flurothyl seizures.

Behavioral characteristics of seizures have age-dependent features, which suggests that effective treatment of seizures may be age-specific as well. In experiments that used the flurothyl seizure model, we examined the effects of several drugs that affect GABAergic neurotransmission in rats of various ages. Systemic administration of phenobarbital (PB, a drug that enhances GABAA receptor-mediated inhibition) was anticonvulsant in most age groups. In contrast, gamma-vinyl GABA (VGB, a drug that increases endogenous GABA levels and enhances both GABAA and GABAB receptor transmission) did not have anticonvulsant effects. Baclofen (a GABAB receptor agonist) was proconvulsant in 9-day-old rat pups, and anticonvulsant in 15-30-day-old rats and lost its anticonvulsant activity in 60-day-old rats. CGP 35348 (a GABAB receptor antagonist) was proconvulsant in developing rats but not in 60-day-old rats. A novel GABAB receptor antagonist, CGP 36742, was proconvulsant in 9- and 15-day-old rats but had no effects in 30- and 60-day-old rats. These results indicate that the effects of presumed GABAergic agents are not uniform across the age span. The differences may reflect age-dependent maturational changes of GABA receptor subtypes, differential action of the drugs on pre- and postsynaptic sites and possible non-GABAergic effects.

Age Factors↗
PubMed1994

Developmental changes of ketamine action against epileptic afterdischarges induced by hippocampal stimulation in rats.

Action of ketamine (5-40 mg/kg) was tested against electrically induced hippocampal afterdischarges (four stimulations in one session; 8 Hz, 15 s) in rats 7, 12, 18, 25 and 90 days old. In control sessions, there was either stable afterdischarge (AD) duration and wet dog shakes (WDS) number or there was an increase in ADs' duration with repeated stimulations. Ketamine had dose-dependent and age-dependent effects. In 7-18-day-old rats, ketamine suppressed better WDS number than AD duration, with nearly absent action on AD duration in 18-day-old animals. Ketamine was equipotent for both phenomena in 25-day-old rats and, in contrast, it decreased more AD duration than WDS number in 90-day-old rats. The data suggest a differentiation induced by ketamine in the expression of motor and electrographic phenomena of the experimental seizures.

Age Factors↗
PubMed1994

Lowering of extracellular pH suppresses low-Mg(2+)-induces seizures in combined entorhinal cortex-hippocampal slices.

Lowering [Mg2+]o induces epileptiform bursting in hippocampus and entorhinal cortex (EC), presumably by activation of N-methyl-D-aspartate (NMDA) receptors. Since increasing [H+]o has been shown to reduce NMDA receptor activation, we hypothesized that this could contribute to anticonvulsant actions of acidic pH. To test this, we studied the effects of raising extracellular PCO2 (20.6%, pH = 6.7) or lowering extracellular pH (6.7 or 6.2) on low-Mg(2+)-induced epileptiform discharges. Lowering the pH to 6.7 by either means increased the interval between seizure-like events (SLEs), decreased the maximal amplitude of SLEs, and if the site of seizure generation was at a distance from the recording site, acidification slowed the rate of seizure propagation. In contrast, the duration of SLEs was unaffected by acidic pH or high PCO2. Raising PCO2 or lowering pH to 6.7 also blocked early (8-10 min) but not late (> 20 min) phases of status-like discharges. All effects of the extracellular pH changes were fully reversible. Further lowering of extracellular pH to 6.2 completely and reversibly blocked both SLEs and status-like discharges. Our data show that the effects of high PCO2 and low pH on seizures in the EC in vitro may be dose-dependent and consistent with induction by proton blockade of NMDA receptors. Thus, blockade of NMDA currents by protons may be an important component of the anticonvulsant action of extracellular acidosis. The results also suggest that acidosis may be a desirable property for new antiepileptic treatments.

Acidosis↗
PubMed1994

Clonidine, but not ritanserin, suppresses kainic acid-induced automatisms in developing rats.

In young rats, systemic or local administration of kainic acid (KA) elicits scratching as the prevailing automatism whereas in adult rats, wet dog shakes (WDS) are usually recorded. We tested the effects of the alpha 2-adrenergic agonist clonidine (0.25 mg/kg, IP; also acting, however, on imidazoline receptors), which has been reported to block KA-induced WDS in adult rats and the 5-HT2 antagonist ritanserin (20 mg/kg, IP) in rats aged 7, 12, 18, 25, and 90 days treated IP with doses of KA that induce maximum number of automatisms with minimal early lethal effects (i.e., 4, 6, 8, 10, and 14 mg/kg, respectively). Both WDS and scratching were frequently recorded together in one animal. Neither ritanserin nor its solvent had significant effects on the total number of automatisms or on their distribution between WDS and scratching. In contrast, clonidine suppressed automatisms throughout the development studied. In 90-day-old (adult) rats clonidine decreased the incidence of both WDS and scratching, whereas it usually attenuated scratching at younger ages. Kainic acid-induced seizures were also recorded because of reported incompatibility between tonic-clonic seizures and WDS in adult rats. In 18-90-day-old rats, tonic-clonic seizures and WDS were found incompatible. In 7-18-day-old pups, scratching and KA-induced tonic-clonic seizures occurred together. Moreover, in 7-day-old rats, clonidine was anticonvulsant. We have demonstrated that KA-induced automatisms develop from scratching in pups to prevailing WDS in adult rats, whereas the incidence of scratching rather decreases during development.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

The development of epilepsy in the paediatric brain.

The immature central nervous system (CNS) is more susceptible to the development of seizures than its adult counterpart. Developmental studies of experimental seizures have suggested that young animals have unique behavioural seizure patterns, including the presence of bilateral, though asymmetric, convulsions. There are differences in the mechanisms responsible for the generation of seizures, propagation patterns and seizure arrest and recurrences. These differences are due to local factors as well as factors that affect neural systems consisting of long neuronal circuits. The substantia nigra, a site involved in the control of seizures, will be used as an example to demonstrate how evolving neurobiological processes modulates the suppression or exacerbation of seizures with age. Evidence will also be presented indicating that early in life, seizures may not produce hippocampal damage. An understanding of the age-related differences is important for the development of rational approaches to treating seizures and their consequences.

Age Factors↗
PubMed1993

Age dependence of homosynaptic non-NMDA mediated long-term depression in field CA1 of rat hippocampal slices.

It has been hypothesized that high levels of presynaptic activity that fail to activate postsynaptic N-methyl-D-aspartate (NMDA) receptors may lead to long-term depression (LTD). Therefore, we tested the ability of high-frequency (50 Hz) synaptic stimulation in the presence of a blocker of NMDA receptors to elicit homosynaptic LTD at Schaffer collateral-CA1 synapses in hippocampal slices from 15-, 30- and 60-day-old rats. In control slices, there were no developmental differences in the incidence of long-term potentiation (LTP) of either EPSP slope or population spike amplitude. However, while NMDA receptor blockade with the specific antagonist D-2-amino-5-phosphonopentanoic acid (AP5; 25 microM) completely eliminated LTP in 30 and 60-day-olds, a significant number of slices from 15-day-old rats displayed some non-NMDA LTP of synaptic transmission. Moreover, under NMDA receptor blockade, the same high-frequency stimulation now induced homosynaptic LTD of population spike amplitude in a significant number of slices from 15- and 60-day-old rats (47% and 42%, respectively) but not in 30-day-olds (7%). LTD of population spike amplitude was most pronounced in 15-day-old slices (27 +/- 6% of baseline), whereas, in 60-day-old slices, LTD was 81 +/- 3% of baseline. LTD of EPSP slopes occurred in 44% of 15-day-olds, 13% of 30-day-olds, and 33% of slices from 60-day-old rats; the magnitude of EPSP was similar in 15 and 60-day-old slices (70 +/- 9% versus 81 +/- 1% of baseline).(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

N-methyl-D-aspartate (NMDA)-induced seizures in developing rats.

Intraperitoneal administration of N-methyl-D-aspartate (NMDA) elicited epileptic motor seizures in developing rats aged from 7 to 25 days as well as in young adults. The very first sign of NMDA action is locomotor hyperactivity which is followed by clonic and tonic seizures. In rat pups during the first 3 postnatal weeks flexion seizures (emprosthotonus) appeared as the first pattern of motor seizures; later they were replaced by generalized tonic clonic seizures. Only regular tonic-clonic seizures were observed in 25-day-old and adult rats. The youngest animals are the most sensitive to NMDA. CD50 for tonic-colonic seizures is 6.7 mg/kg in 7-day-old rat pups and it increases up to 86.6 mg/kg in 25-day-old animals. Similar changes could also be demonstrated for LD50, a lethal outcome being very frequent. EEG recordings demonstrated mainly suppressed activity, thus exhibiting a lack of correlation with motor phenomena.

Aging↗
PubMed1992

Differential effects of naloxone on postictal depression.

The influence of naloxone on the duration of the postictal depression was determined in 2 seizure models in the adult rats: hippocampal afterdischarges and maximal electroshock. For testing the intensity of postictal depression 2 subsequent stimulations were used. The interstimulation intervals were 3, 5, 10 and 60 min. Using interstimulation intervals 3, 5 and 10 min there was marked depression of the afterdischarge duration. Wet dog shakes accompanying hippocampal afterdischarges were suppressed only in 3- and 5-min intervals. Naioxone (1 mg/kg i.p.) abolished the suppression of afterdischarges when 10-min interstimulation interval was used. In maximal electroshock seizures where the duration of tonic flexion and extension was determined, no postictal depression was registered nor were any effects of naloxone present. The results suggest a limited role of the mu opioid receptor system in the late phases of postictal depression following hippocampal stimulation and different effects of the mu opioid system in tonic flexion/extension and behavioral depression induced by maximal electroshock.

Animals↗
PubMed1991

Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis. II. The effects of MK-801.

MK-801 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant and neuroprotective properties. The action of MK-801 (0.05-10 mg/kg IP) was assessed against pentylenetetrazol-induced seizures (PTZ; 100 mg/kg SC; 30 min after MK-801) in rats aged 7, 12, 18, 25, and 90 days (N = 263). We observed pronounced ataxia and hypermobility after MK-801 pretreatment during the whole ontogenesis, and the animals exhibited head-weaving and body-rolls. After the combination of MK-801 and PTZ "wet dog shakes" were detected in 18-, 25-, and 90-day-old rats (never seen in controls receiving PTZ only). MK-801 only insignificantly modified the latencies of minimal (clonic) seizures in 18-day-old and older rats where this seizure type is regularly elicited. In 12-day-old rats an increased incidence of minimal seizures was detected. MK-801 nearly completely blocked or strongly delayed major (generalized tonic-clonic) seizures and attenuated the seizure severity during ontogenesis in a dose-dependent manner. Present results suggest the important role of NMDA receptors in the genesis of generalized tonic-clonic seizures whilst the role of NMDA receptors in minimal seizures appears to be negligible during the whole ontogenetic development.

Aging↗
PubMed1991

Bicuculline-induced neocortical epileptiform foci and the effects of 6-hydroxydopamine in developing rats.

Catecholamines (dopamine and norepinephrine) are considered to be predominantly inhibitory neurotransmitters in the brain and their depletion produced by 6-hydroxydopamine may result in proconvulsant effects. In our experiments on rats aged 5, 7, 9, 12, 15, 18, 25 and 90 days under urethane anesthesia we demonstrated the development of neocortical epileptic focus evoked by topical application of bicuculline methiodide. In experimental groups aged 7, 12, 18, 25 and 90 days a chronic depletion of catecholamines was induced using pretreatment with 6-hydroxydopamine early postnatally. An epileptogenic focus was induced in all age groups; duration of a single discharge decreased with age in both control and experimental animals. The spread of activity from the primary focus to contralateral frontal cortex via callosal connections was as rapid as in controls. However, the transfer of discharge to occipital regions was delayed and the number of discharges decreased in experimental rats. Our study demonstrated a substantial role of catecholamines for synchronization of focal discharges in neocortex and a promoting role of catecholamines in association pathways within neocortex.

Animals↗
PubMed1990

Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis. I. The effects of 2-amino-7-phosphonoheptanoate.

The anticonvulsant action of 2-amino-7-phosphonoheptanoate (AP7) was assessed during ontogenesis of the rat. Animals of five age groups (7, 12, 18, 25, and 90 days) were pretreated with AP7 i.p. in the doses from 15 to 60 mg/kg 30 min prior to pentamethylenetetrazol (PTZ; metrazol; 100 mg/kg s.c.). The incidence and latency of minimal seizures (pure clonic without the loss of righting ability) and of generalized tonic-clonic seizures (major) were evaluated and compared with the control groups. Minimal metrazol seizures were not regularly observed in controls between ages 7 and 12 days. An increased incidence was noticed in AP7-treated groups. In animals of 18 days of age and older the AP7-pretreatment did not influence incidence of minimal seizures; the latencies were significantly lengthened only in 18-day-old animals. Major seizures were significantly suppressed with the highest dose of AP7 (60 mg/kg) in all groups except 7-day-old rats. In 90-day-old rats all doses of AP7 were effective in the suppression of major seizures. The latencies of major seizures were increased in 7 and 18 days old rats. It appears that the blockade of NMDA receptor substantially influences the major seizures induced by PTZ, whereas minimal (clonic) seizures are affected weakly. This suggests an important role of NMDA receptor-mediated transmission in the genesis of generalized tonic-clonic seizure pattern.

2-Amino-5-phosphonovalerate↗